Pigment Yellow FC 26290

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

A reproduction/developmental toxicity screening test in rats to assess general toxicity and potential effects on fertility of the F0 generation as well as potential effects on pre- and early postnatal development of the F1 generation after oral exposure was conducted in compliance with the OECD Guideline for Testing of Chemicals, Section 4: Health Effects No. 421 „Reproduction/Developmental Toxicity Screening Test“, adopted July 27, 1995

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Test Item: Bayplast Gelb G Gran
Synonymes: Pigment Yellow FC 26290
Chemical name: 2-[[5-amino-3-methyl-1-(3-sulfophenyl)- 1H-pyrazol-4-yl]azo]-4,5-dichloro-benzenesulfonic acid, calcium salt 1:1
CAS No.: 111071-53-5
Molecular Mass (g/mol): 544.4 g/mol
Content(s): 86.4%

Test animals

Species:

rat

Strain:

Wistar

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

The F0 animals were pretreated with the test substance for 2 weeks prior to the cohabitation period. During the following cohabitation period the first F0 male was co-housed with the first female F0 animal within the group and so on over night (afternoon up to next morning) at a planned maximum of 14 times during the two-week cohabitation period. As a rule inseminated females were not further co-housed. Insemination was established by investigating vaginal smears prepared in the morning after co-housing or by occurrence of a vaginal plug.

Duration of treatment / exposure:

females: 57 days
males: 36 days

Frequency of treatment:

The test substance or vehicle was administered daily to the animals from the first day of the study until the day before scheduled necropsy.

Duration of test:

57 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 300 or 1000 mg/kg body weight
Basis:
actual ingested

No. of animals per sex per dose:

12 male and 12 female Wistar rats per dose group

Control animals:

yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day

Based on:

act. ingr.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Reproduction parameters did not indicate any effect on male or female reproductive function. In addition, no effects on developmental parameters in F0 females and on parameters measured in F1 pups were found indicating any signs of developmental toxicity.

Evaluation of Implantation Sites in F0 Females

Dose No. of Implantation Sites Total No. of Pups at Birth Prenatal Loss

mg/kg per Litter Total                                                     Means per Litter

0 14.50 116                             106                                   10

100 14.91 164               150                                    14

300 12.86 90               84                                    6

1000 14.60 146               133                                    13

F1 Litter Parameters at Birth and Viability

The total numbers of pups born, stillborn pups, the live birth index, percentage of males born, the litter size at birth and the viability index were not affected by treatment

Dose Number of Pups Live Birth Males Mean Litter Viability on Day 4 p.p.

mg/kg Total Dead Index % % Size 1) %

0 106 8 92.86 53.06 12.25               91.07

100 150 0** 100.00 51.79 13.64               98.64

300 84 5 94.51 58.92 11.29               94.64

1000 133 0** 100.00 45.99 13.30               100.00

1) viable pups only

Clinical Observations in F1 Pups

No clinical signs with a dose-dependent distribution were observed in F1 pups during the five days lactation.

The following findings were considered as spontaneous findings: Several animals of the control group were cold to touch and did not reveal a milk spot. At 100 mg/kg, paleness was observed in one animal and one animal did not reveal a milk spot.

Body Weights of F1 Pups

The weights at birth and on day 4 p.p. of pups were not relevantly changed

Pup Weights in g

Dose in mg/kg Sex Day 0 p.p. Day 4 p.p.

0                      m 6.89 11.64

100               m 6.82 11.52

300               m 7.03 12.59

1000               m 7.12 11.81

0                      f 6.57 11.28

100               f 6.49 11.23

300               f 6.72 12.28

1000               f 6.79 11.40

Gross Pathological Changes in F1 Pups

No macroscopical alterations with a remarkable incidence or dose-dependency were noted at pup necropsies.

Autolysis of parts of the body was observed in few animals. This included 2 control pups (Nos. 9 and 12) as well as 3 pups in the mid dose group (Nos. 10, 11 and 12).

Applicant's summary and conclusion

Executive summary:

Bayplast Gelb G Gran (Pigment Yellow FC 26290_CAS no 111071-53-5)was administered daily via gavage in 0.9% aqueous sodium chloride solution to 12 male and 12 female Wistar rats per dose group, in doses of 0, 100, 300 or 1000 mg/kg body weight. Treatment started 2 weeks prior to mating and continued during the mating period of up to 2 weeks. Males were dosed further up to necropsy for a total period of at least 4 weeks and females were dosed during gestation and lactation up to their necropsy on day 4-6 post partum.

Investigations were performed on general tolerance of the test compound by the parental animals as well as on effects on reproduction including early postnatal development of F1 pups. The animals were regularly observed and weighed, food intake and reproduction parameters were determined. Selected organs were weighed and organs were subjected to macroscopical and histopathological investigations.

The compound did not result in any signs of parental toxicity. The yellow discoloration of the content of the gastro-intestinal tract was a consequence of the administration of the strongly coloured test compound. Body weight and food consumption were not affected. Reproduction parameters did not indicate any effect on male or female reproductive function. In addition, no effects on developmental parameters in F0 females and on parameters measured in F1 pups were found indicating any signs of developmental toxicity.

In conclusion, 1000 mg/kg represents the NOEL for male and female reproductive function and for developmental toxicity.