Poly(oxy-1,2-ethanediyl), α-(carboxymethyl)-ω-hydroxy-, C16-18 (even numbered) and C18-unsatd. alkyl ethers

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

GLP study; considered as reliable by experts groups of HERA and CIR

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Reference 2

Reference Type:

publication

Title:

Human & Environmental Risk Assessment on Alcohol Ethoxylates

Author:

HERA Substance Team

Year:

2009

Bibliographic source:

Web Publication

Reference 3

Reference Type:

publication

Title:

Safety assessment of alkyl PEG ethers as used in cosmetics.

Author:

Cosmetic Ingredient Review (CIR) Expert Panel

Year:

2012

Bibliographic source:

Int J Toxicol. 2012 Sep-Oct;31(5 Suppl):169S-244S

Reference 4

Reference Type:

publication

Title:

Acute, Subchronic, and Reproductive Toxicity of a Linear Alcohol Ethoxylates Surfactant in the Rat

Author:

Gingell and Lu

Year:

1991

Bibliographic source:

Journal of the American College of Toxicology, Volume 10, Number 4, page 477-486

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 416

Deviations:

yes

Remarks:

Only 3 applications per week/ no treatment during mating

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

68439-46-3

EC Number:

614-482-0

Cas Number:

68439-46-3

IUPAC Name:

68439-46-3

Test animals

Species:

rat

Strain:

Fischer 344

Administration / exposure

Route of administration:

dermal

Vehicle:

water

Details on exposure:

Dose volume: 1 mL/kg bw

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

F0 generation: 119 days prior to mating
F1 generation: 133 days prior to mating

Frequency of treatment:

3/week (except during mating)

Duration of test:

P: 119 days of dosing
F1: 133 days of dosing

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Remarks:

dermal exposure to 1mL/kg of 0% test material (w/v) in water

Doses / concentrations 2

Dose / conc.:

10 mg/kg bw/day

Remarks:

dermal exposure to 1mL/kg of 1% test material (w/v) in water

Doses / concentrations 3

Dose / conc.:

100 mg/kg bw/day

Remarks:

dermal exposure to 1mL/kg of 10% test material (w/v) in water

Doses / concentrations 4

Dose / conc.:

250 mg/kg bw/day

Remarks:

dermal exposure to 1mL/kg of 25% test material (w/v) in water

No. of animals per sex per dose:

30 (P)
20/40 (male/female; F1)

Control animals:

yes, concurrent vehicle

Details on study design:

The P0 groups, consisting of 30 males and 30 females, were exposed dermally to 1 mL/kg of 0%, 1%, 10% or 25% w/v aqueous test material 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. Among the F1 generation, groups of 20 males and 20 females per test group were mated. The male rats of both generations were killed following mating.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

effects observed, treatment-related

Description (incidence and severity):

No irritation was observed for any of the animals, but dry flaking skin was observed in the 10% and 25% dose groups.

Mortality:

mortality observed, non-treatment-related

Description (incidence):

Five death was observed in the F1 adult in the ctronol and treatment group, not treatment related

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Minimal decrease at 25%.

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

Weight change in liver, lung, kidney and heart in P1/F1 animals

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Maternal developmental toxicity

Other effects:

no effects observed

Description (incidence and severity):

No effects regardin mating indices, fertility indices, or mean gestational length.

Effect levels (maternal animals)

1

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

>= 250 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: No significant effect up to the highest dose level

Remarks on result:

other:

Remarks:

The NOAEL obtained in a two generation reproduction toxicity study

2

Key result

Dose descriptor:

NOAEL

Remarks:

reproductive performance

Effect level:

>= 250 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: No significant effect up to the highest dose level

Remarks on result:

other:

Remarks:

The NOAEL obtained in a two generation reproduction toxicity study

Results (fetuses)

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Remarks:

developmental

Effect level:

>= 250 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: Up to 250 mg/kg bw no significant effect onthe growth and developmental of the offspring was found in the two generation reproduction toxicity study

Fetal abnormalities

Key result

Abnormalities:

no effects observed

Overall developmental toxicity

Key result

Developmental effects observed:

no

Applicant's summary and conclusion

Executive summary:

In a GLP-compliant 2-generation reproduction study, groups of thirty weanling rats of each sex were treated dermally with 1 mL/kg bw of C9-11AE6 at concentration of 0, 1, 10 or 25% w/v (0, 10, 100 or 250 mg/kg bw/d) three times a week except during the mating periods. No compound related effects on litter size, number of live pubs and sex ratio of pups in the F1 and F2 generations were observed. Low incidences of foetal malformations were observed, but these were not dose related and considered to be of spontaneous nature. At necropsy, no effects were observed in the F1 pups. In the F2 pups, a significantly higher carcass weight in the females of the 250 mg/kg bw/d dose group was noted and some minor organ weight differences. Due to the lack of a doseresponse and no associated morphological findings, these effects were considered to be of no toxicological significance. It was concluded that dermal application of C9-11AE6 to rats did not induce any adverse effects on the growth and development of the offspring during two generations. The NOAEL of C9-11AE6 with respect to developmental and teratogenic toxicity can be assumed to be higher than the highest dose level dermally applied in this study (i.e., 250 mg/kg bw/d)