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Key value for chemical safety assessment

Effects on fertility

Description of key information

No reliable data regarding fertility is available for Pigment Red 48:1(Ba). Based on studies performed with members of the same category it can be concluded that Pigment Red 48:1(Ba) does not affect fertility.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
Please see the category read-across justification in the category object.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Dose descriptor:
NOAEL
Remarks:
Reproduction
Effect level:
> 1 000 mg/kg bw/day
Based on:
other: read-across
Sex:
male/female
Basis for effect level:
other: no adverse effects expected
Dose descriptor:
NOEL
Remarks:
systemic
Effect level:
< 100 mg/kg bw/day
Based on:
other: read-across
Sex:
male/female
Basis for effect level:
other: no adverse effects expected
Dose descriptor:
LOEL
Remarks:
systemic
Effect level:
40 mg/kg bw/day
Based on:
other: read-across
Sex:
female
Basis for effect level:
other: no adverse effects expected
Critical effects observed:
yes
Lowest effective dose / conc.:
40 mg/kg bw/day (nominal)
System:
urinary
Organ:
kidney
Treatment related:
yes
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 1 000 mg/kg bw/day
Based on:
other: read-across
Sex:
male/female
Basis for effect level:
other: no adverse effects expected
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No reliable data regarding fertility is available for Pigment Red 48:1(Ba). Experimental data is available for the calcium and sodium salt analogues as well as Pigment Red 53:1 (also a Barium containing Pigment Red).

 

Pigment Red 57:1(Ca) caused no effects on fertility in a valid screening study performed according to OECD testing guideline 422 at doses of 100, 300, and 1000 mg/kg bw/day (MHLW 1993). Up to the highest dose of 1000 mg/kg bw, no indication on female or male fertility were observed. The 14-day pre-mating period allows only a limited assessment of male fertility, but further information on male fertility can be derived from the fertility element and the histopathology of the long term feeding study with the sodium salt of Pigment Red 57. The fertility element is similar to the one-generation study (OECD 415) with the limitation that 60 instead of 70 days treatment prior to mating are used. No adverse effects on fertility or reproductive organs were observed at dose levels in the diet of up to 2%. This study is adequate in design and reporting for hazard assessment. Discoloration of urine by the test item indicates systemic availability despite the better water solubility compared to Pigment Red 57:1(Ca).

 

Results regarding a three-generation study with Pigment Red 57:1(Ca) in rats are mentioned in various secondary sources. The actual study (Weil 1973) was performed following a non-standard design with doses of 0.5, 5, 15 and 50 mg/kg bw. Rats are treated via the feed for three generations and each generation produced one to three sets of offspring which were used for mating or pathology. Historical control data was not available. Analysis in the feed was not performed. Limited details are reported regarding macroscopic and microscopic examinations. The study reports effects on fertility for males of the second generation at 50 mg/kg bw, but not of the first or third generation. Histopathology investigations on reproductive organs were apparently not performed for the F2 generation. Detailed data is only given for the three control groups and the high dose group of the F1b group regarding lung, liver, kidney, heart, adrenal, thyroid, trachea and prostate. The findings of the three-generation study are poorly reported and inconclusive and therefore do not contribute to hazard assessment. No effects on lactation were observed.

 

The chlorinated analogue Pigment Red 48:2(Ca) was also tested in a GLP-compliant screening study performed according to OECD testing guideline 422 at doses of 40, 200 and 1000 mg/kg bw. Pigment Red 48:2(Ca) had no effects on the reproductive parameters such as estrous cycle, mating index, fertility index, delivery index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, or parturition or maternal behaviour. On the examination of neonates, there were no significant differences in the number of offspring or live offspring, sex ratio, live birth index, or viability index on day 4. No abnormal findings attributed to the test substance were found in external features, clinical signs, body weights, or necropsy of the offspring.

The OECD SIDS document of barium bis[2-chloro-5-[(hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (Pigment Red 53:1) describes a study which appears to be identical in design to the one-generation study with Pigment Red 57:1(Ca). No adverse effects were recorded for reproductive toxicity indeces at 10000 ppm in the feed. Parental toxicity consistent with other repeated dose studies of this pigment was observed.

Effects on developmental toxicity

Description of key information

No reliable data regarding developmental toxicity is available for Pigment Red 48:1(Ba). Based on studies performed with members of the same category it can be concluded that Pigment Red 48:1(Ba) is not a developmental toxicant.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
Please see the category read-across justification in the category object.
Reason / purpose for cross-reference:
read-across source
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day
Based on:
other: read-across
Basis for effect level:
other: no adverse effects expected
Abnormalities:
no effects observed
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (actual dose received)
Based on:
other: read-across
Sex:
male/female
Basis for effect level:
other: no adverse effects expected
Abnormalities:
no effects observed
Developmental effects observed:
no
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Study reports are available for two teratogenicity studies with Pigment Red 57:1(Ca) in rats and in rabbits (Durloo 1972). The study in rabbits is of limited value as only 10 pregnant females per dose group were used. Pregnant rabbits received 5, 16 or 50 mg/kg bw by gavage during gestation days 6 - 18 and they were sacrificed on gestation day 29. No effects were recorded regarding the number of viable and dead fetuses, resorption sites, mean fetal weight, distribution of sex, mean litter size, frequency of skeletal anomalies and frequency of visceral and structural anomalies.

 

The study in rats was performed with doses of 5, 16 and 50 mg/kg bw, applied by gavage during gestation days 5 to 15. No adverse effects were reported regarding the same endpoints as for rabbits. The study included limited investigations regarding maternal toxicity, as only body weight gain of dams was reported. No individual data and no statistical evaluation are given in the report. The highest dose is slightly above the subacute NOAEL for adverse effects on kidney.

 

Furthermore, no indication of developmental toxicity was observed in the OECD 422 screening studies with Pigment Red 57:1(Ca) and 48:2(Ca) (MHLW 1993 and 2009).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity according to Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008.

Additional information