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Toxicological information

Developmental toxicity / teratogenicity

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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:
other: Data is from peer- reivewed journal

Data source

Reference
Reference Type:
publication
Title:
THE TERATOGENIC POTENTIAL IN RATS AND RABBITS OF D&C YELLOW NO.8
Author:
C. M. Burneti, Clairol R & D Laboratory, Stamford, Ct 06902 And E.L.Goldenthal
Year:
1986
Bibliographic source:
Fd Chem. Toxic, Vol. 24, No. 8, pp. 819 823, 1986

Materials and methods

Principles of method if other than guideline:
The teratogenic potential was determined in Sprague dawley rats after the administration of D & C Yellow No. 8 by gavage
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Solid
Details on test material:
- Name of test material (as cited in study report): D & C Yellow No. 8 or acid yellow 73
- Molecular formula (if other than submission substance):• 1.C20H10Na2O5
•2. C20H10O5.2Na
•3. C20H12O5.2Na
- Molecular weight (if other than submission substance): 376.274g/mole
- Substance type: Organic
- Physical state: Solid
- Analytical purity: 87%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, Michigan
- Age at study initiation: 14 weeks
- Weight at study initiation:No data available
- Fasting period before study:No data available
- Housing:No data available
- Diet (e.g. ad libitum):No data available
- Water (e.g. ad libitum):No data available
- Acclimation period: 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72 ± 4F
- Humidity (%): 50 ± 15%
- Air changes (per hr): No data avaialble
- Photoperiod (hrs dark / hrs light): 2-hrlight/dark cycle

IN-LIFE DATES: From: To:No data available

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
From day 6-19 days of gestation
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- M/F ratio per cage: No data available
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Copulatory plug or presence of sperm in vaginal washings.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)]: No
- After successful mating each pregnant female was caged (how): They were housed individually and offered Purina Certified Rodent Chow No. 5002 and water ad lib.
- Any other deviations from standard protocol: Not mentioned
Duration of treatment / exposure:
14 days
Frequency of treatment:
Daily
Duration of test:
days 6-19 of gestation
No. of animals per sex per dose:
Total: 100
0 mg/Kg bw: 25
100 mg/Kg bw: 25
500 mg/Kg bw: 25
1500 mg/Kg bw: 25
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Caesarean sections were performed on all surviving females killed with carbon dioxide on gestation day 20 The number and location of viable and non-viable foetuses, early and late resorptions, total implantations and corpora lutea were recorded.
Ovaries and uterine content:
Gravid and Nongravid uteri were examined.
Fetal examinations:
Foetal sex ratio, foetal body weight, gross pathology and histopathology were examined.
Statistics:
Differences in the Ibctal scx distribution and the number of litters with malformations between control and treated groups wcre compared using the Chi-square test criterion with Yates" correction for 2 x 2 contingency lables and, or Fisher's exact probability test as described by Sicgel (1956). The numbers of early and late resorptions, dead foetuses and post-implantation losses were compared between groups by the Mann Whitney U test as described by Siegel (1956) and Well (1970). The mean numbers of viable foetuses, total implantations, corpora lutca and mean t\)etal weights were compared between groups by analysis of variance (oneway classification), Bartlett's test l\~r homogeneity of variances, and the appropriate t test (for equal or unequal variances) as described by Steel & Torric (1960) using Dunnctt's multiple comparison tables (1964).
Indices:
Dams with viable foetuses, Viable foetuses/dam, Post-implantation loss, Total implantations and Corpora lutea were examined.
Historical control data:
No data available

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Mortality:
when treated wtih 1500 mg/kg bw, Six rats died as compared to control.

Clinical sign:
Orange discoloration of the urine was observed in 100, 500 and 1500 mg/kg bw treated rats.

Body weigth gain:
Slight decrease in body weight gain were observed in 1500 mg/kg bw treated rats as compared to control.

Reproductive indices:
No effect on dams with viable foetuses, viable foetuses/dam, post-implantation loss, total implantations, corpora lutea and number of litters with malformations were examined.

Gross pathology:
Green discoloration of the amniotic fluid was observed in 1, 10 and 16 rats in the 100, 500 and 1500 mg/kg/day treated rats as compared to control.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 500 mg/kg bw/day
Based on:
test mat.
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 effect on Foetal sex ratio, foetal body weight, gross pathology and histopathology were observed.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effect on foetal body weight, sex retio, gross pathology and histopathology

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Mean maternal body weights changesfor rats given D & (" Yellow No. 8 by gavage on days 6 -19 of gestation

 

Day of gestation

       No. of foetuses (no. of litters)

 

0

100mg/kg

500mg/kg

1500mg/kg

0

246±145    

249 ± I3.7

5249±14.7

241±12. 4

6

272±16.8

271 ± 14.4

276±14.5

263 ± 12.2

9

279±18,1

278 ± 15.9

283±16.7

269 ±16.5

12

294±20.1

292 ± 17.5

296 ± 16.1

282 ±16.9

16

321±23.4

320 ± 18.9

323 ± 20.4

300 ± 30.7

20

379±30.0

378 ±21.2

374 ±32.2

359 ±33.3

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1500 mg/kg bw when Sprague-Dawley Female rats were treated with D & C Yellow No. 8 orally by gavage from day 6-19 of gestation.
Executive summary:

In a teratogenic potential study, Sprague-Dawley Female rats were treatedw with D & C Yellow No. 8 in the concentration of 0, 100, 500 and 1500mg/kg body weight orally by gavage. Six rats died at 1500 mg/kg bw as compared to control. Orange discoloration of the urine was observed in 100, 500 and 1500 mg/kg bw treated rats and Slight decrease in body weight gain were observed in 1500 mg/kg bw treated rats as compared to control. Green discoloration of the amniotic fluid was observed in 1, 10 and 16 rats in the 100, 500 and 1500 mg/kg/day treated rats as compared to control. But, no effect on dams with viable foetuses, viable foetuses/dam, post-implantation loss, total implantations, corpora lutea and number of litters with malformations were examined in treated rats as compared to control. In addition, No significant effect on Foetal sex ratio, foetal body weight, gross pathology and histopathology were observed. Therefore, NOAEL was considered to be 1500 mg/kg bw when Sprague-Dawley Female rats were treated with D & C Yellow No. 8 orally by gavage from day 6-19 of gestation.

Based on the observations these doses did not result in evidence of maternal toxicity or adverse effects on foetal development.