Amines, C12-18-alkyl, reaction products with acrylic acid, sodium salts

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted similarly to OECD test guideline 414 with acceptable restrictions. The study was performed on a formulation containing an analogue substance (for justification of read-across, please refer to the corresponding assessment report in Section 13).

Data source

Reference

Reference Type:

publication

Title:

Teratology and percutaneous toxicity studies on hair dyes.

Author:

C. Burnett. E. I. Goldenthal, S. B. Harris, F. X. Wazeter. J . Strausburg, R. Kapp, R. Voelker.

Year:

1976

Bibliographic source:

Journal of Toxicology and Environmental Health, 1: 1027-1040, 1976.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

Only one dose was tested. The animals were treated once every three days during the gestation period instead of daily.

GLP compliance:

no

Remarks:

study conducted before GLP implementation

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium N-(2-carboxyethyl)-N-dodecyl-β-alaninate

EC Number:

239-032-7

EC Name:

Sodium N-(2-carboxyethyl)-N-dodecyl-β-alaninate

Cas Number:

14960-06-6

IUPAC Name:

Sodium Lauriminodipropionate

Test material form:

other: liquid

Details on test material:

- Common name : Sodium lauriminodipropionate
- For more details, see below the Confidential details for test material

Test animals

Species:

rat

Strain:

other: CD

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: individually (the mated females)
- Diet (e.g. ad libitum): ad libitum (Ralston Purina Laboratory)
- Water (e.g. ad libitum): ad libitum (Ralston Purina Laboratory)
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled during the study.
- Humidity (%): controlled during the study.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

dermal

Type of inhalation exposure (if applicable):

other: not applicable

Vehicle:

water

Details on exposure:

TEST SITE
- Area of exposure: the dorso-scapular area.
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: 1 day

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data

TEST MATERIAL
- Concentration (if solution): 20 mL/Kg


USE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: no data
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Any other deviations from standard protocol: no data

Duration of treatment / exposure:

Days 1, 4, 7, 10, 13, 16 and 19 of gestation

Frequency of treatment:

Once every three days during the gestation period

Duration of test:

From gestation day 1 to 20 (sacrifice)

No. of animals per sex per dose:

20 pregnant rats/dose

Control animals:

yes, concurrent no treatment

other: A positive control group received acetylsalicylic acid by gavage at a dose of 250 mg/kg on days 6 through 16 of gestation.

Details on study design:

No data

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: no data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data


BODY WEIGHT: Yes
- Time schedule for examinations: determined on days 1, 4, 7, 10, 13, 16 and 19 of gestation.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: no data

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Number if live and dead fetus: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one-third per litter
- Skeletal examinations: Yes: two-third per litter
- Head examinations: No data

Statistics:

The number of females exhibiting resorption sites, number of females exhibiting two or more resorptions, number of dead or resorbed fetuses, and the number of fetuses with soft-tissue or skeletal anomalies and accessory ribs was compared using chi-square test criterion or Fisher's exact probability test.
The mean number of corpora lutea, implantation sites, live fetuses, and resorption sites was compared by analysis of variance using Dunnett's multiple comparison tables to judge the significance of differences.
Statistically significant differences between groups were judged valid only when there were significant diffences between the dye treated group and each of the three untreated controls groups.

Indices:

No data

Historical control data:

Not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
- No signs of toxicity were seen throughout the study, except for the changes in the color of the skin and hair at the site of dye application. No irritation or other changes in appearance were seen.
- Changes in female body weights were similar for rats in the untreated controls and the treated group. A marked reduction in maternal weight gain through gestation was observed in the rats receiving acetyl-salicylic acid (positive control) as compared with either the untreated control rats or dye-treated rats.
- Mean food consumption for all groups (treated + untreated) throughout gestation was similar except for rats in the acetylsalicylic acid group; these rats showed a moderates decrease in food consumption from days 7 to 13 of gestation. This decrease was not seen from days 13 to 20 of gestation.

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

2 other: mL/Kg

Based on:

other: test formulation containing 1.5% of Sodium lauriminodipropionate

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- No significant differences were observed between the treated and untreated groups in the mean number of corpora lutea, implantation sites and live fetuses and the sex ratio.
- No differences between groups were seen regarding the number of females exhibiting resorption sites or mean resorptions per pregnancy. No significant changes were observed regarding soft-tissue anomalies between the dye-treated group and the untreated control groups.
- The skeletal variations observed in this study was accessory ribs. However, this variation was more frequent in the untreated animals than the treated group.
- Increase in teratogenicity, increase in embryo-death and decrease in fetal weight were observed in the positive control group.

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

2 other: mL/Kg

Based on:

other: test formulation containing 1.5% of Sodium lauriminodipropionate

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Table 7.8.2/2. Summary of Teratology Study in Rats receiving p-23 (test formulation containing 1.5% of Sodium lauriminodipropionate)

Observations	Control I untreated	Control II untreated	Control III Iuntreated	Acetylsalicylic acid (250 mg/kg-day)	P-23 (2mL/Kg) (test formulation containing 1.5% of Sodium lauriminodipropionate)
Maternal parameters
Total no. females gravid	20	20	20	20	20
Mean no. corpora lutea	15.35	13.55	15.25	16.15	14.80
Mean no. implantation sites	12.4	12.10	13.90	13.25	13.50
No. females exhibiting resorption sites	13	14	12	15	12
No. females exhibiting 2 or more resorption sites	9	7	6	15	6
No. females aborting	0	0	0	0	0
Fetal parameters
Mean no.live fetuses/group	10.65	10.85	12.5	8.70	12.15
Mean live fetal weight (g)	3.38	3.58	3.62	2.89	3.96
No. dead or resorbed fetuses (%)	35 (14.11)	25 (10.33)	28 (10.07)	91 (34.34)	27 (10.00)
Mean no. resorptions/pregnancy	1.75	1.25	1.4	4.55	1.35
Sex ratio, M: F	106:107	102:115	119:131	100:75	123:120
No. fetuses with soft-tissue anomalies (%)	4 (6.35)	4 (6.06)	6 (7.79)	21 (36.84)	9 (12.16)
No. fetuses with skeletal anomalies (%)	0 (0.00)	1 (0.67)	2 (1.16)	40 (34.19)	3 (1.78)
No. fetuses with accessory ribs only (%)	75 (50.00)	56 (37.09)	72 (41.62)	32 (27.35)	66 (39.05)

 

Applicant's summary and conclusion

Conclusions:

Under the test conditions of this study, no embryotoxic or teratogenic effects were observed in the CD rats following dermal application of formulation P-23 containing 1.5% of sodium lauriminodipropionate, once every three days over the gestation period.

Executive summary:

In a developmental toxicity study, one hair dye formulation containing 1.5% of sodium lauriminodipropionate was administered topically to groups of 20 CD female rats at a dose level of 2 mL/kg on days 1, 4, 7, 10, 13, 16 and 19 of gestation. Pilot study had shown that the potential skin irritancy would not permit more frequent application. Three negative control groups were tested in this study. The positive control group received acetylsalicylic acid by gavage at a dose of 250 mg/kg on days 6 through 16 of gestation.

Twenty pregnant rats from each group were sacrificed on day 20 of gestation, and Cesarean sections were performed.

No signs of toxicity were seen throughout the study, except for the changes in the color of the skin and hair at the site of dye application. No irritation or other changes in appearance were seen. Changes in female body weights were similar for rats in the untreated controls and the treated group. A marked reduction in maternal weight gain through gestation was observed in the rats receiving acetyl-salicylic acid (positive control) as compared with either the untreated control rats or dye-treated rats. Mean food consumption for all groups (treated + untreated) throughout gestation was similar except for rats in the acetylsalicylic acid group. These rats showed a moderates decrease in food consumption from days 7 to 13 of gestation. This decrease was not observed from days 13 to 20 of gestation.

No significant differences were observed between the treated and untreated groups in the mean number of corpora lutea, implantation sites and live fetuses and the sex ratio. No differences between groups were seen regarding the number of females exhibiting resorption sites or mean resorptions per pregnancy. No significant changes were observed regarding soft-tissue anomalies between the dye-treated group and the untreated control groups. The skeletal variation observed in this study was accessory ribs. However, this variation was more frequent in the untreated animals than the treated group. Increase in embryo-death and decrease in fetal weight were observed in the positive control group.

Under the test conditions of this study, no embryotoxic or teratogenic effects were observed in the CD rats following dermal application of formulation P-23 containing 1.5% of sodium lauriminodipropionate, every every three days over the gestation period.