Laureth-4

The Basics On Laureth-4

What is Laureth-4?

Derived from lauryl alcohol and used either as a surfactant or emulsifier.

What are other names for Laureth-4?

3,6,9,12-TETRAOXATETRACOSAN-1-OL, LAURETH-4, LAURYL ALCOHOL TRI(OXYETHYLENE) ETHANOL, PEG-4 LAURYL ETHER, POLYETHYLENE GLYCOL 200 LAURYL ETHER, POLYOXYETHYLENE (4) LAURYL ETHER, and TETRAETHYLENE GLYCOL DODECYL ETHER

What is Laureth-4 used for?

In cosmetics and personal care products, laureth-4 functions as a surfactant and emulsifier. It can be found in products such as bath, cleansing, hair, and sunscreen products. … This allows surfactants to attract and suspends oils, dirt, and other impurities that have accumulated on the skin and wash them away.

How Laureth-4 is classified

Thickeners/Emulsifiers, Texture Enhancer, Cleansing Agents

Recommendations for using Laureth-4 during pregnancy and breastfeeding

Limited data suggests no known risk

 

Laureth-4 During Pregnancy

What we know about using Laureth-4 while pregnant or breastfeeding

Limited information available.

A two-generation reproductive study was performed using Fischer 344 rats to examine whether C9-11 pareth-6 had any effect on reproductive parameters.45 The F0 groups, consisting of 30 males and 30 females, were exposed dermally to 1 ml/kg of 0, 1, 10 or 25% w/v aq. C9-11 pareth-6 for 119 days prior to mating. The test site was shaved, but the application sites were not covered. The test material was not applied during mating to avoid ingestion. For the second generation, after 133 days of dosing, groups of 20 males and 20 females per test group were mated. For both generations, the application sites were evaluated for irritation. The male rats of both generations were killed following mating. Gross necropsies were performed on all F0 and F1 parents and on 5 pups/gender/dose. There was no mortality in the F0 generations, and deaths that did occur in the F1 generation were not attributed to treatment. No irritation was observed for any of the animals, but dry flaking skin was observed in the 10 and 25% dose groups. For effects on body weight, 10% was a no-effect level and 25% C9-11 pareth-6 caused a minimal decrease in body weights over the study. There were no compound-related effects on maternal body weights in any test group. No toxicologically significant effects were observed regarding organ weights, mating indices, fertility indices, or mean gestational length, CIR Panel Book Page 62 21 and dermal administration of the test compound did not have an effect on the growth or development of the offspring. A decrease in the number of sperm in the high dose F0 males was not considered treatment-related or toxicologically significant. Oral Laureths The reproductive and teratogenic toxicity of compounds analogous to laureth-9 was evaluated.33 Groups of 25 gravid female rabbits were dosed orally with 0, 50, 100, or 200 mg/kg bw C12AE6 on days 2-16 of gestation, and the animals were killed and necropsied on day 28 of gestation. In the 100 and 200 mg/kg groups, ataxia and a slight decrease in body weights was evidence of maternal toxicity. No effects on reproductive parameters were noted. Nine control animals and 1 test animal died during the study. Based on maternal toxicity, the NOAEL was >50 mg/kg bw/day. Groups of 25 male and 25 female CD rats were used to evaluate the reproductive toxicity of C14-15AE7 in a twogeneration study. The animals were fed a diet containing 0, 0.05, 0.1, and 0.5% of the test article (equivalent to approximately 0, 25, 50, and 250 mg/kg bw/day). In three test groups, males and females were given treated feed throughout the study; in another three groups, females only were dosed, and dosing was performed on days 6-15 of gestation. (Additional details regarding study and dosing regimen were not provided.). No compound-related differences in fertility, gestation, or viability indices were observed, and the NOAEL for reproduction with dietary administration of C14-15AE7 was >0.5% (equivalent to 250 mg/kg bw/day). In addition, effects on the FC generation, i.e. offspring from the third mating of the F0 and F1 parenteral generation, were examined. Gravid female rats were necropsied and examined on either day 13 or day 21 of gestation. Differences in maternal and fetal indices were observed in the test groups compared to the controls, but these effects were not considered test-compound related. Parental female rats and pups of the high-dose group had reduced body weight gains. In the 0.5% continuous feeding test group, increased mean liver weights of males and females of the P1 generation and an increase in relative liver to body weights of males of the 0.5% continuous feeding group of the P2 generation at 60 days were considered compound-related. The NOAEL for maternal and developmental toxicity was 50 mg/kg bw/day. The reproductive toxicity of C12AE6 was evaluated in a similar study, and the animals were fed 0, 25, 50, or 250 mg/kg bw/day of the test article in the diet. No treatment-related effects on behavior, appearance, survival, or fertility were observed in any of the test groups. Parental and offspring weight gain was reduced in the 250 m/kg group. In the 250 mg/kg group, statistically significant increases in embryo lethality and soft tissue anomalies were observed, and in the 50 mg/kg group, a statistically significant decrease in mean fetal liver weights was observed. None of these effects were considered test article-related. The NOAEL for reproduction was >250 mg/kg bw/day, and the NOAELs for maternal and developmental toxicity were 50 mg/kg bw/day C12AE6 in the diet. PEG Methyl Ethers In a modified Chernoff-Kavlock test, groups of 10 gravid Alpk:AP Wistar rats were dosed daily by gavage with 250 or 1000 mg/kg PEG-3 methyl ether (99.9+%) at a volume of 10 ml/kg on days 7-16 of gestation.40 The negative control group of 10 gravid rats was given 10 ml/kg water and the 2 positive control groups were dosed with 50 and 250 mg/kg methoxyethanol. The dams were allowed to deliver their pups. Treatment-related effects were not seen in either the dams or the pups as a result of dosing with 250 or 1000 mg/kg PEG-3 methyl ether, as compared to the negative controls. All dams of the negative control and PEG-3 methyl ether groups delivered live fetuses. None of the positive control animals delivered any litters. Groups of gravid CD (SD) rats (number not stated) were dosed orally by gavage with 0, 300, 1650, or 3000 mg/kg PEG-3 methyl ether on day 6 of gestation to post-natal day (PND) 21.57 The litters were culled to 8 pups on PND 4, and 1 CIR Panel Book Page 63 22 male and 1 female pup from each litter was killed on PNDs 22 and 68. The only maternal dose-related effects reported were increased length of gestation and in increase in kidney weight at the highest dose. Birth weight of females in the mid dose group and males and females in the high dose group were significantly increased compared to controls. However, post-natal weight gains were decreased at various times. No effects on motor activity were observed. The developmental toxicity of PEG-3 methyl ether (99.27% purity) was evaluated using rats and rabbits.38 Gravid Crl:CD (SD) BR rats, 25 per group, were dosed orally by gavage with 625, 1250, 2500, or 5000 mg/kg on days 6-15 of gestation, and the animals were killed on day 20 of gestation. A negative control group was given deionized water by gavage. In the high dose group, clinical signs of toxicity, such as decreased motor activity, excess salivation, ataxia, and impaired righting reflex, were statistically significantly increased and occurred with the first or second dose of 5000 mg/kg PEG-3 methyl ether. One rat in this group, which was actually non-gravid, died on day 13; no treatment-related effects were seen at necropsy. No signs of toxicity were seen in the other dose groups. Maternal body weights, gravid uterine weights, and feed consumption were statistically significantly reduced in the high dose group, and feed consumption was statistically decreased in the 2500 mg/kg group on days 12-16 of gestation. Pregnancy rates were not affected, but embryo lethality was statistically significantly increased in the high dose group. Fetal body weights were statistically significantly decreased in the 2500 and 5000 mg/kg group and slightly decreased in the 1250 mg/kg group. The incidence of gross external, soft tissue, or skeletal fetal malformations was not affected at any dose level. Doses of ≥1250 mg/kg PEG-3 methyl ether did cause significant increases in reversible delayed ossification. The maternal and developmental no-observable effect levels (NOELs) for rats were 625 mg/kg/day PEG-3 methyl ether. The NOAEL for maternal toxicity in the rat was 1250 mg/kg/day. Gravid NZW rabbits, 20 per group, were also dosed orally with PEG-3 methyl ether. Doses of 250, 500, 1000, or 1500 mg/kg were given by stomach tube on days 6-18 of gestation, and the animals were killed on day 29 of gestation. A negative control group was dosed with deionized water. In the high dose group, clinical signs of toxicity, such as decreased motor activity, labored breathing, reddish brown staining of the anogenital area and a red substance in the cage, appeared near the end of dosing, and the incidence was statistically significant. Mortality was also statistically significantly increased for this group; 8 does died during days 17-21 of gestation. Gastric ulcerations, observed at necropsy, were also statistically significantly increased for this group. Treatment-related effects were not seen in the other dose groups, but one doe of the 1000 mg/kg groups died on day 18 of gestation. Maternal weight gain was decreased for the high dose group during dosing, but a rebound effects occurred during the post-treatment period, leading to significantly increased body weight gains. The average uterine weight was decreased in the high dose group as compared to controls. Feed consumption was decreased throughout dosing. Again, a rebound effect was seen post-dosing, and feed consumption was increased in the 500 mg/kg group and statistically significantly increased in the 1000 and 1500 mg/kg groups. Oral administration of PEG-3 methyl ether did not affect pregnancy rates, average number of corpora lutea or implantation sites, or mean fetal body weights, and it did not cause any gross external, internal soft tissue, or skeletal malformations. Decreased live litter sizes and increased resorption rates in the 1000 and 1500 mg/kg groups occurred, but were not statistically significant. Fetal and/or litter incidence of two common skeletal variations, angulated hyoid alae and reversible delayed ossification of the xiphoid, were statistically significantly increased in the 1500 mg/kg group. For rabbits, the maternal and developmental toxicity NOELs were 250 and 1000 mg/kg/day PEG-3 methyl ether, respectively. The NOAEL for maternal toxicity was 500 mg/kg/day, and the presumed NOAEL for developmental toxicity was 1500 mg/kg/day. CIR Panel Book Page 64 23 Groups of 64 gravid female Sprague-Dawley rats were dosed orally, by gavage, with 0, 300, 1650, or 3000 mg/kg/day PEG-3 methyl ether (99.2% purity) on days 6-21 of gestation in a study of developmental neurotoxicity.20 The pups were delivered, litters were culled on day 4, and the offspring were observed in a number of tests. One male and one female pup from each litter were killed on post-natal days (PNDs) 22 and 68. In maternal animals, no dose-related patterns of clinical signs of toxicity or mortality were noted, and there were no significant differences in body weights between test and control animals. Kidneys weights of maternal rats were statistically significantly increased in high dose dams compared to controls. A maternal NOAEL of 1650 mg/kg bw was assigned. The length of gestation was statistically significantly increased in animals of the high dose group; however, the researchers found the biological significance of this questionable. Body weights of female pups of the mid and high dose groups and male pups of the high dose group were significantly greater than controls at PND 0. At PND 68, male pups of the high dose group weighed statistically significantly less than controls. Male pup development, determined by time of testes descent, was significantly advanced in pups of the mid and high dose groups; no treatment-related effects for this observation were found at necropsy. Behavioral evaluations did not find any dose-related effects on motor activity or active avoidance. A significant effect on auditory startle response parameters was noted; the significance of this finding was not clear to the researchers. The researchers assigned an NOEL of 300 mg/kg for offspring, while EPA assigned an NOAEL of 300 mg/kg for teratogenicity. GENOTOXICITY Laureths Laureth (chain length not specified) was tested in a number of genotoxicity studies. In an Ames study, laureth (3- 333 µg/plate) was negative with and without activation.58 In a standard transformation assay with BALB/c-3T3 cells, laureth (tested at 0.00132-0.0417 and 0.00625-0.0250 mM) was inactive.59 Using Chinese hamster ovary (CHO) cells, laureth did not induce sister chromatid exchanges (concentrations of 3.08-10.8 µg/ml with or 0.308-3.08 µg/ml without metabolic activation) or chromosomal aberrations (5-50 µg/ml with or without activation).60 In a L5178Y mouse lymphoma cell mutation assay (0-50 nl/ml with and 0-40 nl/ml without activation), the results were suggestive of a lack of mutagenic activity; one test without metabolic activation produced questionable results, and one with metabolic activation had inconclusive results.61 In a mouse bone marrow micronucleus assay, laureth was not genotoxic when tested at doses of 31.25-125 mg/kg.62 Compounds that are analogous to laureth-9 were not mutagenic in the Ames test at concentrations of ≤5000 µg/plate or clastogenic in a chromosomal aberration assay using CHO cells at concentrations of ≤25 µl/ml, with or without metabolic activation.33 In vivo, 1.7 g/kg of a 20% solution and 2.5 g/kg active ingredient of a 10% solution did not induce chromosomal aberrations in Chinese hamsters. A dose of 1000 mg/kg was not clastogenic in Wistar rats. PEG Methyl Ethers The mutagenicity and genotoxicity of aq. PEG-3 methyl ether (99.23% purity) was evaluated in an Ames test using four strains of S. typhimurium at concentrations ≤5000 µg/plate with and without metabolic activation, in an HGPRT forward mutation assay in CHO cells at concentrations of ≤5000 µg/plate with and without metabolic activation, and in an in vivo mouse micronucleus test at concentrations of ≤5000 mg/kg.20 The results were negative in all three studies. Expected results were seen with appropriate negative and positive controls. CIR Panel Book Page 65 24 The mutagenic potential of PEG-7 methyl ether was evaluated using an Ames assay.21 Concentrations of 1-110 mg/plate were tested using five strains of Salmonella typhimurium, with and without metabolic activation. PEG-7 methyl ether was not mutagenic at any dose. C9-11 Pareths The mutagenic potential of ≤1 mg/plate C9-11 pareth-6 was evaluated in an Ames test using S. typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 in the presence and absence of metabolic activation.45 The appropriate positive controls were used with each strain to validate the study. Toxicity occurred at higher concentrations (actual doses not specified) in all strains, but there were no mutagenic responses to C9-11 pareth-6, with or without metabolic activation. CARCINOGENICITY Laureths The carcinogenic potential of compounds analogous to laureth-9 was evaluated.33 Groups of 65 rats/gender were fed a diet containing 0, 0.1, 0.5, and 1% C14-15AE7 for 2 yrs. At 1 yr, 14-15 animals per gender were killed and necropsied. No compound-related changes were seen in behavior or appearance at any time. Survival rate was comparable between test and control animals. Body weight gains were significantly decreased in females of the 0.5 and 1.0% groups and males of the 1% group. At necropsy, no differences in relative or absolute organ weights were observed between test and control animals. There was no evidence of a carcinogenic effect. C12-13AE6.5 was fed to 100 Sprague-Dawley rats at concentrations up to 1% in feed for 2 yrs. Feed consumption, and correspondingly, body weight gain, was reduced for females fed 0.5 or 1% and for males fed diets containing 1% of the test compound. No microscopic effects were seen, and C12-13AE6.5 was not carcinogenic.

General safety info about Laureth-4 from CIR

The CIR Expert Panel assessed the safety of Alkyl PEG Ethers used in cosmetics. These 369 ingredients function in cosmetics primarily as surfactants. The undeceths, laneths, and hydrogenated laneths also function as skin conditioning agents, the oleths as fragrance ingredients, and the sec-pareths as emulsion stabilizers. Some do not function as surfactants. For example, the PEG methyl ethers function as solvents and humectants, and the PEG propylheptyl ethers as emulsion stabilizers. The Panel reviewed the relevant animal and clinical data from both previous CIR reports as well as that found in an updated search. The Panel concluded that the Alkyl PEG Ethers are safe as used when formulated to be non-irritating, and the same applies to future alkyl PEG ether cosmetic ingredients that vary from those ingredients recited herein only by the number of ethylene glycol repeat units.

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Products where you might find Laureth-4

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