Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: 0.5 % (w /v)methylcellulose (MC) solution
Duration of treatment / exposure:
42 days
Frequency of treatment:
daily
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
40 mg/kg bw/day
Dose / conc.:
200 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
Control animals:
yes, concurrent vehicle
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects
Critical effects observed:
no
No general or systemic toxicity was seen in treated males and females. No test article-related changes were observed in estrous cycle examination, copulation rate, copulatory interval, fertility rate, gestation index, gestation period, number of corpora lutea, number of implantations, implantation index, live birth index, delivery index, or nursing behavior in any test article group.
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall no effects observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
The no-observed-aclverse-effect level (NOAEL)of Disperse Blue 77 was judged to be 1000 mg/kg/day for reproductive and developmental toxicity because no changes were observed in reproductive function or in any pup.
Executive summary:

Disperse Blue 077 was evaluated for reproductive and developmental toxicity in a study conducted according OECD to TG 422. In this study, the test substance was repeatedly administered  orally  to  12 Crl:CD(SD) male rats (10 weeks old at the initiation of dosing) per group at dose levels of 0 [0.5 w/v% methylcellulose (MC) solution], 40, 200, and 1000 mg/kg/day once daily for 14 days. The animals were then mated to observe reproductive ability, and the toxic changes induced over 42-day repeated oral administration were evaluated. Disperse Blue 77 was also repeatedly administered orally to 12 Crl:CD(SD) female rats (10 weeks old at the initiation of dosing) per group at the same dose levels as males from 14 days before mating through the mating and gestation periods until Day 4 of lactation to evaluate reproductive ability and viability and development of pups. For the control and 1000 mg/kg groups, a 2-week recovery period was set to follow the 42-day repeated oral administration, to assess the reversibility of the toxicity. No animal died in any test article group. No general or systemic toxicity was seen in treated males and females. No test article-related changes were observed in estrous cycle examination, copulation rate, copulatory interval, fertility rate, gestation index, gestation period, number of corpora lutea, number of implantations, implantation index, live birth index, delivery index, or nursing behavior in any test article group. With respect to examinations of pups, no test article-related changes were noted in the number of pups delivered, number of live pups, live birth index, viability index or sex ratio on Day 0 after birth, number of live pups, viability index or sex ratio on Day 4 after birth, clinical signs, external examinations, body weight, or necropsy. Accordingly, it is considered that the test article does not affect the development or growth of next generation. From these results, under the conditions of  this study,  the no-observed-aclverse-effect level (NOAEL) of Disperse Blue 077 was judged to be 1000 mg/kg/day for reproductive and developmental toxicity because no changes were observed in reproductive function or in any pup.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,8-dihydroxy-4-nitro-5-(phenylamino)anthraquinone
EC Number:
243-632-4
EC Name:
1,8-dihydroxy-4-nitro-5-(phenylamino)anthraquinone
Cas Number:
20241-76-3
Molecular formula:
C20H12N2O6
IUPAC Name:
1,8-dihydroxy-4-nitro-5-(phenylamino)anthraquinone

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % (w/v) methylcellulose (MC)-solution
Duration of treatment / exposure:
42 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
40 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
The no-observed-adverse-effect level (NOAEL) of Disperse Blue 077 was judged to be 1000 mg/kg/day for general toxicity.
Executive summary:

Disperse Blue 077 was evaluated for reproductive and developmental toxicity in a study conducted according to OECD TG 422. In this study, the test substance was repeatedly administered  orally  to  12 Crl:CD(SD) male rats (10 weeks old at the initiation of dosing) per group at dose levels of 0 [0.5 % (w/v) methylcellulose (MC)-solution], 40, 200, and 1000 mg/kg/day once daily for 14 days. The animals were then mated to observe reproductive ability, and the toxic changes induced over 42-day repeated oral administration were evaluated. Disperse Blue 077 was also repeatedly administered orally to 12 Crl:CD(SD) female rats (10 weeks old at the initiation of dosing) per group at the same dose levels as males from 14 days before mating through the mating and gestation periods until Day 4 of lactation to evaluate reproductive ability and viability and development of pups. For the control and 1000 mg/kg groups, a 2-week recovery period was set to follow the 42-day repeated oral administration, to assess the reversibility of the toxicity. No animal died in any test article group. In clinical signs, test article-colored feces were observed in all test article groups, and colored aqueous solution and retention of content was observed in the gastrointestinal tract at necropsy. In the 1000 and 200 mg/kg groups, discoloration (test article-like color) was observed in the mucosa in the stomach, ileum, cecum, and colon. ln blood chemistry, low total protein, low albumin, and high alpha-2-globulin were noted after dosing in males in the 1000 mg/kg group. However, these changes were judged to be toxicologically insignificant because no differences from the control group were noted in any examination after the completion of the recovery period, and no changes were noted in any female. In urinalysis, in males, changes in urine color which were considered lo have reflected the color of the test article or its metabolite were noted in all animals in the 1000 and 200 mg/kg groups. No test article-related changes were noted in detailed observations, grip strength, locomotor activity, body weight, food consumption, hematology, organ weight, necropsy, or histopathology in any group. From these results, under the conditions of  this study,  the no-observed-effect  level (NOEL) of Disperse Blue 077 was judged to be 40 mg/kg/day for general toxicity in consideration of the discoloration of the mucosal surface of the gastrointestinal tract and abnormal urine color observed in the 200 mg/kg group. The no-observed-adverse-effect level (NOAEL) of Disperse Blue 077 was judged to be 1000 mg/kg/day for general toxicity because changes observed in parental animals were toxicologically insignificant.