Benzophenone

The Basics On Benzophenone

What is Benzophenone?

Group of compounds used in cosmetics as sunscreen agents and to help prevent the other product ingredients from degrading under UV light. Oxybenzone is a derivative of benzophenone.

What are other names for Benzophenone?

A-OXODIPHENYLMETHANE, A-OXODITANE, BENZENE, BENZOYL-, BENZOPHENONE, BENZOYL- BENZENE, BENZOYLBENZENE, DIPHENYL KETONE, DIPHENYL- METHANONE, DIPHENYLMETHANONE, METHANONE, DIPHENYL, METHANONE, DIPHENYL-, and PHENYL KETONE

What is Benzophenone used for?

In personal care products, benzophenone is used as a fragrance enhancer or to prevent products such as soaps from losing scents and colors in the presence of UV light. Derivatives of benzophenones such as BP2 and oxybenzone (BP3) are used in sunscreens.

How Benzophenone is classified

Sunscreen Actives

Recommendations for using Benzophenone during pregnancy and breastfeeding

Limited data suggests no known risk

 

Benzophenone During Pregnancy

What we know about using Benzophenone while pregnant or breastfeeding

Limited information available.

In Vitro Benzophenone-3 The embryotoxicity of Benzophenone-3 was evaluated in the fish embryotoxicity test using zebrafish embryos.74 The test was performed in accordance with a modification of OECD TG 236. The applied number of zebrafish embryos was 40 at each concentration in 4 replicates. The experiment was prolonged until 120 h post-fertilization, because this period includes time points at which different developmental states can be observed. The following 6 concentrations of Benzophenone-3 (in dimethylsulfoxide (DMSO)) were prepared: 0.116 mM, 0.0789 mM, 0.0523 mM, 0.0307 mM, 0.0219 mM, and 0.00535 mM. Each solution was supplemented by a certain volume of DMSO in order to achieve the same DMSO concentration (3.52 mM; 250 ¬µl/l). The positive control was 3,4-dichloroaniline (0.0247 mM), and water served as the negative control. DMSO served as the solvent control. The following endpoints were evaluated: mortality, malformations, hatching, and inflation of the swim bladder. Cumulative mortality was under 10% in the negative and solvent control groups at the end of the experiment. In the positive control group, cumulative mortality was 75%. In the negative and solvent control groups, the percentage of hatched embryos was 95%. No hatched embryos were observed in the positive control group. Except for one in the solvent control group (no swim bladder was observed), there were no malformations in the negative and solvent control groups. The following LC50 values were reported: 0.0766 mM (at 72 h post-fertilization), 0.0698 mM (at 96 h), and 0.0573 mM (at 120 h). At a concentration of 0.00438 mM, all embryos were able to inflate their swim bladder. However, at higher concentrations, Benzophenone-3 caused the absence of swim bladder inflation in a concentration-dependent manner. The calculated EC50 value was 0.0295 mM after 120 h post-fertilization. At 72 h post-fertilization, deformation of the tail was observed (EC50 = 0.0419 mM). Additionally, malformation of the somites was observed at concentrations of 0.0526 and 0.0789 mM. Benzophenone-3 decreased the number of hatched embryos after 96 h post-fertilization. The EC50 value was 0.0543 mM. Other malformations (not named) were observed, but the incidence was not concentration-dependent. These included pericardial and yolk sac edema, deformed jaw and ventricle or dilated gut, and jaw deformity. The authors concluded that Benzophenone-3 caused mortality, unsuccessful hatching, and different malformations to zebrafish. Distributed for Comment Only — Do Not Cite or Quote The effect of Benzophenone-3 on follicular assembly was studied using whole ovary cultures collected from Wistar rats.75 Ovaries (n = 120) were collected from rats at birth (postnatal day 0). Pups from the same litters were randomly assigned to different treatment groups so that each group contained ovaries of different pups from different litters. The ovary cultures were treated for 7 d with the following Benzophenone-3 concentrations (in (DMSO): 5.8 nM, 276 nM, 576 nM, and 876 nM. Vehicle control cultures were treated with 0.01% DMSO. Positive control cultures were treated with the estrogen receptor Œ≤ (ESR2) antagonist, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo-1,5-Œ±-pyrimidin-3-yl) phenol (PHTPP) in DMSO. Exposure to 5.8 mM Benzophenone-3 decreased the population of total oocytes and decreased the number of early primary follicles. Benzophenone-3 (276 mM) increased the population of total oocytes, but decreased the number of primary follicles. Thus, these results indicate that exposure to a low concentration of Benzophenone-3 (5.8 mM) stimulated the process of germ cell nest breakdown and caused a decrease in the reserve of total oocytes. Exposure to a higher concentration (276 nM) caused the opposite effect. In ovaries exposed to even higher concentrations of Benzophenone-3 (576 nM and 876 nM), no changes were observed in the number of oocytes, germ cell nests per ovary, and assembled follicles in ovaries. Animal Dermal Benzophenone-3 In a 13-wk dermal dosing study, B6C3F1 mice (10 males and 10 females per group) received topical doses of 22.75 to 364 mg/kg in acetone. 71 Epididymal sperm density was decreased at all 3 dose levels evaluated (22.75, 91.0, and 364.0 mg/kg). Therefore, it was not possible to establish a NOAEL for decreased epididymal sperm density. A study was performed to analyze whether dermal exposure to Benzophenone-3 during pregnancy affects the outcome of a second pregnancy in mice. 76 Pregnant mice (number not stated) were exposed dermally to Benzophenone-3 (50 mg/kg/d) or olive oil (vehicle) from GD 0 to 6. High-frequency ultrasound imaging was used to follow fetal and placental growth in vivo. Blood flow parameters in uterine and umbilical arteries were analyzed by Doppler measurements. The mice were killed on GD 5, 10, and 14 (during first pregnancy), and on GD 10 and 14 (during second pregnancy). Benzophenone-3 levels were analyzed in serum and amniotic fluid. Benzophenone-3 dosing resulted in reduced fetal weight at GD 14 and feto-placenta index (first pregnancy), with 16.13% of fetuses under the 5th percentile; uterine artery parameters showed an altered pattern at GD 10. Benzophenone-3 was detected in serum 4 h after exposure on GD 6, and in amniotic fluid, on GD 14. The weight of offspring of the first progeny was lower in the group dosed with Benzophenone-3. Placental weights in animals dosed with Benzophenone-3 were decreased in the second pregnancy. First and second progenies of mothers exposed to Benzophenone-3 showed a higher percentage of females (female sex ratio). Dermal exposure to Benzophenone-3 during early pregnancy resulted in an intrauterine growth restriction (IUGR) phenotype, disturbed sex ratio, and alterations in the growth curve of the offspring in the mouse model. Oral Benzophenone-1 The reproductive toxicity of Benzophenone-1 was evaluated using female rats (number and strain not stated).6 The test substance was administered orally for 3 d. Details relating to the test protocol were not included. A NOAEL of 10 mg/kg/d was reported. Regarding observations of any reproductive effects, the authors noted that reproductive effects were not specified. Benzophenone-2 The developmental toxicity of Benzophenone-2 (in 10% ethanol/90% corn oil vehicle) was evaluated using groups of 5 timed pregnant C57BL/6NCr mice.77 Benzophenone-2 (6.25 mg) was administered via gavage on GD 12 through 17. Control pregnant mice were dosed with vehicle only. The animals were killed on GD 18. The anogenital distance in male fetuses was measured and genital tubercles were examined histologically. Quantitative reverse transcriptase-polymerase chain reaction analysis of genes purportedly involved in genital tubercle development was also performed. In the test group, 8 of 57 male fetuses had hypospadias (p = 0.0064, when compared to controls). When compared to controls, there were no changes in body mass-adjusted anogenital distance. The co-administration of Benzophenone-2 with an estrogen receptor antagonist (10 ¬µg in vehicle (subcutaneously (s.c.)) during gestation, yielded normal genital tubercles; i.e., no hypospadias in 26 of 26 mice. Hypospadias was not observed after dosing with the estrogen receptor antagonist only or after dosing with vehicle only. Reverse transcriptase-polymerase chain reaction analysis showed that genital tubercles of Benzophenone-2-treated male mice had higher levels of estrogen receptor-Œ≤, when compared to male controls (p = 0.04). The authors concluded that Benzophenone-2 may cause hypospadias via signaling through the estrogen receptor. Benzophenone-3 Benzophenone-3 (administered in feed) was tested for its effects on fertility and reproduction in Swiss CD-1 mice, according to the continuous breeding protocol.78 Based on the results of a dose-finding study, 1.25%, 2.5%, and 5.0% (w/w) were chosen to investigate effects on fertility and reproduction. Male and female mice were continuously exposed for a 7-d Distributed for Comment Only — Do Not Cite or Quote precohabitation and a 98-d cohabitation period. The feed consumption in the 2.5 and 5.0% groups was consistently higher, but the F0 body weights were consistently lower. These findings suggest that Benzophenone-3 may be adversely affecting metabolism or the digestive process in Swiss CD-1 mice. In the 2.5 and 5.0% Benzophenone-3 dose groups, the number of live pups per litter was significantly reduced. The F1 generation from control, 2.5%, and 5.0% groups were weaned for second generation studies. During lactation and nursing of F1 pups, pup survival was significantly below the control value in the 2.5 and 5.0% groups. Benzophenone-3 had minimal effects on fertility in the F1 generation, but pup weights were significantly reduced. Epididymal sperm motility, sperm count, and percentage of abnormal sperm were not affected by Benzophenone-3 treatment. Additionally, there were no apparent effects on estrual cyclicity or the average estrous cycle length in treated females. Based on the results of the present study, it was concluded that Benzophenone-3 caused systemic toxicity, but had minimal effects on fertility and reproduction. In a 13-wk oral dosing study, B6C3F1 mice (10 males and 10 females per group) received feed containing 0, 3125, 6250, 12,500, 25,000, or 50,000 ppm Benzophenone-3. 71 Mice in the highest dose group (50,000 ppm in feed) exhibited a decrease in epididymal sperm density and an increase in length of the estrous cycle. The effects of oral exposure to Benzophenone-3 on growth and morphology of the mammary gland and anogenital distance was evaluated using 3 groups of mated BALB/c female mice. 79 From pregnancy day 0 until the day before weaning (lactational day 21), the females were dosed orally with Benzophenone-3 (in tocopherol-stripped corn oil). The following doses were administered: 30 ¬µg/kg/d, 212 ¬µg/kg/d, and 3000 ¬µg/kg/d. Thus, the offspring were exposed in utero, and via lactation. Sample sizes for the treatment groups were: 30 ¬µg/kg/d (10 litters), 212 ¬µg/kg/d (11 litters), and 3000 ¬µg/kg/d (9 litters). The sample size for controls was 11 litters. Pups were weaned on postnatal day 21 and co-housed with same-sex animals of the same treatment group for the remainder of the experiment. Developmental exposures to Benzophenone-3 reduced the size and growth of the mammary gland in males prior to (at postnatal day 21, statistically significant reduction) and during puberty (reduction not statistically significant). In females, Benzophenone-3 reduced mammary cell proliferation (statistically significant at 30 ¬µg/kg/d), decreased the number of cells expressing estrogen receptor Œ± (statistically significant at 30 or 212 ¬µg/kg/d), and altered mammary gland morphology (dose response) in adulthood. In males, the anogenital index was reduced after exposure to 30 and 212 ¬µg/kg/d at postnatal day 21 and in puberty. In adult males, no differences in anogenital distance were observed. No effect on male body weight was observed. In females, the anogenital index was unaffected at postnatal day 21, but decreased (at 212 ¬µg/kg/d) when measured at puberty. No effects of Benzophenone-3 exposure on female anogenital index were observed in adulthood. In a 13-wk oral dosing study, F344/N rats (10 males and 10 females per group) received diets containing 0, 3125, 6250, 12,500, 25,000, or 50,000 ppm Benzophenone-3.71 Rats receiving a diet with 50,000 ppm Benzophenone-3 showed markedly lower epididymal sperm density and an increase in the length of the estrous cycle at the end of the study. A study was performed to determine the effects of maternal and lactational exposure to Benzophenone-3 on the development of offspring.42 Groups (7 to 8 animals per group) of mated female Sprague-Dawley rats were fed the following Benzophenone-3 concentrations (in low-phytoestrogen chow) from GD 6 until weaning on postnatal day 23: 1000; 3000; 10,000; 25,000; or 50,000 ppm. The control group was fed the low-phytoestrogen chow only. No exposure-related clinical signs were observed. On GD 10, 15, and 20, the body weights of dams decreased in a dose-dependent manner. Absolute and relative kidney weights in dams were statistically significantly higher in the 50,000 ppm exposure group, when compared to the control group. Exposure to Benzophenone-3 was associated with reduced body and organ weights in male and female offspring. There were no statistically significant differences in the mean number of implantation sites/litter, mean resorptions per litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and Benzophenone-3 dose groups. One fetus in the 50,000 ppm group had hydrocephaly, but no other malformations were observed. Normalized anogenital distance in male pups at postnatal day 23 was decreased in the 50,000 ppm exposure group. Exposure to this concentration also caused impairment of spermatocyte development in the testes of male offspring. In females, follicular development was delayed in the 50,000 ppm exposure group. The authors concluded that few adverse effects in rat dams and offspring dosed maternally and lactationally with Benzophenone-3 (in chow) from GD 6 to postnatal day 23 were observed at Benzophenone-3 concentrations of 10,000 ppm or less. At higher concentrations, it is possible that Benzophenone-3 produced a delay in postnatal growth, which could have adversely affected reproductive organ development; however, this is not clear. The authors noted that further work is needed to clarify the possible decreases in spermatogenesis and folliculogenesis observed in this study. Groups of 25 pregnant Sprague-Dawley rats were fed low-phytoestrogen chow containing 3000 or 30,000 ppm Benzophenone-3 from GD 6 until postnatal day 21.80 The male offspring , evaluated in this study, were then weaned on postnatal day 28, and subsequently dosed with Benzophenone-3 via chow and milk. Daily observation of male offspring did not reveal any clinical observations related to perinatal Benzophenone-3 exposure. At necropsy on postnatal day 30, body weights were 22% lower in the 30,000 ppm Benzophenone-3 exposure group when compared to the control group (diet without Benzophenone-3). Rats exposed perinatally to 30,000 ppm Benzophenone-3 also had statistically significantly lower weights of the paired-testis, paired-epididymis, and prostate. These weights were lower in males exposed to 30,000 ppm Distributed for Comment Only — Do Not Cite or Quote Benzophenone-3 when compared to controls (26%, 17.6%, and 18.5%, respectively). The paired-testis weight to body weight ratio was also statistically significantly lower in the 30,000 ppm exposure group; however, there were no changes in the relative weights of the paired epididymis and prostate in the 30,000 ppm Benzophenone-3 exposure group. Rats exposed to Benzophenone-3 did not have any differences in seminal vesicle weight. Serum testosterone concentrations in rats exposed perinatally to 3000 and 30,000 ppm Benzophenone-3 were 13.5% and 28.3% lower when compared to controls, with statistical significance obtained in the 30,000 ppm Benzophenone-3 exposure group. Also, the liver and paired-kidney weights were lower in a dose-dependent manner in the 30,000 ppm Benzophenone-3 exposure group, attaining statistical significance. However, relative liver and paired-kidney weights were similar to controls. Results relating to developmental toxicity are included in an NTP oral carcinogenicity study on Benzophenone-3 involving male and female Sprague-Dawley rats.73 On GD 6, groups of 42, 35, 35, and 43 F0 time-mated female rats were fed diets containing 0, 1000, 3000, and 10,000 ppm Benzophenone-3, respectively, for 39 d. Groups of 50 (1000 and 3000 ppm) or 60 (0 and 10,000 ppm) F1 rats per sex continued on study after weaning, and were fed diets containing the same exposure concentrations for 105 wk; 10 F1 rats per sex from the 0 and 10,000 ppm groups were evaluated at 14 wk. Dietary concentrations of 1000, 3000, and 10,000 ppm Benzophenone-3 resulted in average daily doses of approximately 70, 206, and 660 mg Benzophenone-3/kg body weight/d during gestation, and 157, 478, and 1609 mg/kg/d over lactation days (LD) 1 – 14. Gestation body weights of dams receiving 10,000 ppm Benzophenone-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3000 or 10,000 ppm Benzophenone-3 in the diet displayed slight decreases in GD 6 – 21 body weight gain (~10%) relative to the control group, which attained statistical significance. Lower body weight gain over the GD 6 – 9 (10,000 ppm) and 18 – 21 (3000 and 10,000 ppm) intervals, which was associated with slightly lower feed consumption over the GD 18 – 21 interval, likely contributed to this response. The authors noted that these collective effects are minimal and would not be expected to affect normal development of the offspring. The administration of Benzophenone-3 had no effects on the percentage of mated females producing pups, litter size, pup sex distribution, or numbers of male or female pups. The authors noted that the apparent decrease in the percentage of females pregnant in the 10,000 ppm group can be attributed to the 7 animals that had no evidence of pregnancy, as shown by the absence of implantation sites. Therefore, the lower pregnancy rate was not exposure-related, given that exposure began after implantation. Dams receiving Benzophenone-3 did not display any adverse clinical findings before or after parturition. Litter size of the 10,000 ppm Benzophenone-3 group was slightly lower on postnatal days 7 and 10. Benzophenone-3 was evaluated for developmental toxicity in accordance with OECD TG 414, using groups of 25 mated Wistar rats of the Crl:WI (Han) strain.9 Benzophenone-3 (in corn oil) was administered at doses of 40, 200, and 1000 mg/kg/d (once daily, by gavage) on days 6 through 19 post-coitum. The dose volume was 5 ml/kg. The animals were killed on day 20. All fetal pathological findings were indicative of a minor disturbance and delay in ossification at the highest dose tested (1000 mg/kg/d). No test substance-induced effects on fetal morphology were observed at doses of 40 or 200 mg/kg/d. In all dose groups, there was a scattered occurrence of a few external, soft tissue, and skeletal malformations without a consistent pattern. These findings also occurred without a clear dose-response relationship and/or incidence, and were not test substance-related. External variations were not observed in any fetuses in the study. The authors concluded that Benzophenone-3 did not possess any selective teratogenic properties. The NOAEL for Benzophenone-3 was 200 mg/kg/d. Benzophenone-4 In a study involving groups of 26 Wistar rats (13 males, 13 females/group), Benzophenone-4 was administered orally (in corn oil, by gavage) at doses of 750, 1000, and 1250 mg/kg/d. 7 Control rats were dosed with corn oil only. The study was performed in accordance with OECD TG 422. Male rats were treated 2 wk before mating and thereafter for a total of 48 d of dosing. Female rats were treated 2 wk before mating, during mating, during gestation and during lactation, for a total of approximately 63 d of dosing. Recovery groups of male and female rats (5/sex/dose) were treated at 0 or 1250 mg/kg body weight/d for 66 d total. Animals in the recovery groups were allowed to recover for 2 wk after the final dose was given. No morbidity was observed. Estrous cyclicity was unaffected by treatment. All female rats showed evidence of copulation after the cohabitation/mating period. Pregnancy rates were 77, 62, 77, and 77% at 0, 750, 1000, and 1250 mg/kg, respectively. No significant effects were observed on gestation length or litter size. Likewise, no significant effects were observed on the number of live births, pup survival, pup weight or sex ratio. Four pups in the 750 mg/kg dose group were cannibalized. All other pups at 0, 750, 1000, and 1250 mg/kg were normal externally. The internal examination of the pups revealed no test substance-related abnormalities. Microscopic examination of the pups‚Äô thyroid and parathyroid glands in the 0 and 1250 mg/kg dose groups revealed no abnormalities. The NOAEL (reproductive toxicity) for Benzophenone-4 in this study was established at 1250 mg/kg/d. Benzophenone-12 The developmental toxicity of Benzophenone-12 (in 0.5% carboxymethylcellulose suspension in drinking water + 5 mg/100 ml Tween 80) was evaluated using groups of 50 Wistar rats (25 males, 25 females).5 The test substance was administered by gavage at doses of 100, 300, and 1000 mg/kg/d. The groups were dosed daily, from implantation to one day Distributed for Comment Only — Do Not Cite or Quote prior to the expected day of parturition (GD 6 to 19). The female rats were killed on GD 20, and fetuses were removed from the uterus. Neither clinical signs nor effects on body weight (or organ/body weight ratios) were observed. Furthermore, no test substance-related necropsy findings were observed after dosing of dams. There was no evidence of dead/aborted fetuses or pre- and post-implantation loss. Test substance-related external, skeletal, or visceral malformations were not observed. The NOAEL for maternal and prenatal developmental toxicity was 1000 mg/kg/d. Benzophenone-12 (in 0.5% carboxymethylcellulose suspension in drinking water + 5 mg/100 ml Tween 80) was administered by gavage to groups of Wistar rats (F0 animals: 12 males, 12 females/group) at doses of 100, 300, and 1000 mg/kg/d. 5 The control group (12 males, 12 females) was dosed with vehicle only. The duration of treatment was described as follows: 10-wk premating period (males), 2-wk premating period (females), 2-wk mating period (both sexes), ~2 d post-mating (males), entire gestation period, up to 30 d (corresponding to 21 d of lactation and up to 9 d post-weaning), and 35 d postmating (for sperm-negative females). Pups from the F1 litter were selected (F1 rearing animals) for specific post-weaning examinations. The study ended with terminal sacrifice of the F1 rearing animals. All F0 parental animals were also killed. Parental results are described in the Short-Term Toxicity section of this safety assessment. Clinical examinations of F0 parental animals did not reveal any test substance-related adverse findings, and there were no effects on reproductive performance. No test substance-related adverse findings at clinical or gross examination of F1 pups were observed. For F1 rearing animals, there were no test substance-related findings during clinical examinations and sexual maturation, and there were no gross findings. The NOAEL for reproductive performance and fertility of the F0 parental rats and developmental toxicity in the offspring was 1000 mg/kg/d.

General safety info about Benzophenone from CIR

No report found.

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Products where you might find Benzophenone

Virtue Refresh Purifying Leave-In Conditioner; Virtue Create Texturizing Spray; Virtue Mini Create Texturizing Spray