Registration Dossier

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Read Across approach used to analogue substance. Assumption that target substance will have the same properties. Available data fro the source subtance Solvent Red 19E:

Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, oral (gavage), rat (Wistar Han) M/F, OECD guideline 422, GLP: NOAEL = 160 mg/kg bw/day

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH : Please see attached Read Across supporting document in Section 13 which includes the following:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
3. ANALOGUE APPROACH JUSTIFICATION
4. DATA MATRIX
Reason / purpose:
read-across source
Clinical signs:
effects observed, treatment-related
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Food efficiency:
effects observed, non-treatment-related
Water consumption and compound intake (if drinking water study):
effects observed, non-treatment-related
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
effects observed, non-treatment-related
Behaviour (functional findings):
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
effects observed, treatment-related
Key result
Dose descriptor:
NOAEL
Effect level:
160 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: decreased number of pups per litters, decreased number of corpora lutea, decreased number of implantations, decreased fertility index and gestation index
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Ophthalmological findings:
not examined
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
160 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: decreased number of pups per litters, decreased number of corpora lutea, decreased number of implantations, decreased fertility index and gestation index
Reproductive effects observed:
not specified
Conclusions:
Based on read across to an analogue substance, The value of NOAEL (No Observed Adverse Effect Level) for reproduction and development of pups was predicted to be
160 mg/kg body weight/day for both males and females. The value was established based on the decreased number of pups per litter, decreased number of corpora lutea, decreased number of implanatations, decreased fertility index in males and females and gestation. The Target subtance Solvent Red 19T is expected to have the same properties as the tested analogue substance Solvent Red 19E.
Executive summary:

A read across approach was used to predict the reproductive toxicity properties of Solvent Red 19T ( 1-({2-methyl-4-[(2-methylphenyl)diazenyl]phenyl}diazenyl)-N-tridecylnaphthalen-2-amine).

The analogue source substance was Solvent Red 19E, which has the same structure, but where the tridecyl group has been replaced with a 2 -ethyl hexyl group. This material was assessed for reproductive toxicity according to guideline OECD 422. Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.

Wistar rats were dosed at 160, 400, 1000 mg/kg of body weight /day of Solvent Red 19E.

Reproduction

The course of mating, pregnancy and lactation of parental animals, weights of reproductive organs and pituitary gland, spermatogenesis and sperm parameters, microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation, post­ implantation and post-natal losses of mothers and number, weight, sex ratio and development of pups were not adversely affected by the test substance treatment at the lowest dose level. The number of females achieving pregnancy, total number of pups, mean weight of litters and fertility index were slightly decreased.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of prostate gland in males and ovaries, vagina, mammary gland and uterus in females were detected at the dose level 160 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

The course of mating, pregnancy and lactation, weights of reproductive organs, spermatogenesis, microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation losses of mothers and pathological examination of pups were not adversely influenced by the test substance treatment at the dose level 400 and 1000 mg/kg/day.

The number of females achieving pregnancy was decreased at the middle dose level. Calculation of reproduction parameters (significantly decreased number of corpora lutea and decreased number of uterus implantations) and fertility parameters (decreased fertility and gestation index) in animals showed mild changes at the middle dose level.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of prostate gland in males and ovaries, vagina and uterus in females were detected at the dose level 400 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

The number of females achieving pregnancy was decreased at the highest dose level. Examination of number and weight of pups (decrease of mean number of pups per litter and significant decrease of mean weight of litters), calculation of fertility parameters (decreased fertility index) in animals found out changes at the highest dose level.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of ovaries, vagina and uterus in females were detected at the dose level 1000 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

 

The test substance administration had no adverse effect on mortality, growth of animals and some reproduction parameters - course of mating, pregnancy and lactation, spermatogenesis and microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation losses of mothers and pathological examination of pups.

 

The test substance treatment affected the number of pups (decrease of mean number of pups and mean weight of litters, decreased number of corpora lutea and uterus implantations). The mean weight of pups was unchanged.

 

The value of NOAEL (No Observed Adverse Effect Level) for the reproduction and for development of pups was established as 160 mg/kg body weight/day. The value was established on the basis decreased number of pups per litter, decreased number of corpora lutea, decreased number of implantations, decreased fertility index in males and females and gestation index. In males no effect on reproduction was observed.

 

Based on the similarity in structure and manufacturing process, Solvent Red 19T would be expected to have the same properties, and the same NOAEL. (160mg/kg).

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
160 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is GLP compliant and has Klimisch score 1. The quality of the database is therefore considered to be good.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A read across approach was used to predict the reproductive toxicity properties of Solvent Red 19T ( 1-({2-methyl-4-[(2-methylphenyl)diazenyl]phenyl}diazenyl)-N-tridecylnaphthalen-2-amine).

The analogue source substance was Solvent Red 19E, which has the same structure, but where the tridecyl group has been replaced with a 2 -ethyl hexyl group. This material was assessed for reproductive toxicity according to guideline OECD 422. Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.

Wistar rats were dosed at 160, 400, 1000 mg/kg of body weight /day of Solvent Red 19E.

Reproduction

The course of mating, pregnancy and lactation of parental animals, weights of reproductive organs and pituitary gland, spermatogenesis and sperm parameters, microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation, post­ implantation and post-natal losses of mothers and number, weight, sex ratio and development of pups were not adversely affected by the test substance treatment at the lowest dose level. The number of females achieving pregnancy, total number of pups, mean weight of litters and fertility index were slightly decreased.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of prostate gland in males and ovaries, vagina, mammary gland and uterus in females were detected at the dose level 160 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

The course of mating, pregnancy and lactation, weights of reproductive organs, spermatogenesis, microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation losses of mothers and pathological examination of pups were not adversely influenced by the test substance treatment at the dose level 400 and 1000 mg/kg/day.

The number of females achieving pregnancy was decreased at the middle dose level. Calculation of reproduction parameters (significantly decreased number of corpora lutea and decreased number of uterus implantations) and fertility parameters (decreased fertility and gestation index) in animals showed mild changes at the middle dose level.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of prostate gland in males and ovaries, vagina and uterus in females were detected at the dose level 400 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

The number of females achieving pregnancy was decreased at the highest dose level. Examination of number and weight of pups (decrease of mean number of pups per litter and significant decrease of mean weight of litters), calculation of fertility parameters (decreased fertility index) in animals found out changes at the highest dose level.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of ovaries, vagina and uterus in females were detected at the dose level 1000 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

 

The test substance administration had no adverse effect on mortality, growth of animals and some reproduction parameters - course of mating, pregnancy and lactation, spermatogenesis and microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation losses of mothers and pathological examination of pups.

 

The test substance treatment affected the number of pups (decrease of mean number of pups and mean weight of litters, decreased number of corpora lutea and uterus implantations). The mean weight of pups was unchanged.

 

The value of NOAEL (No Observed Adverse Effect Level) for the reproduction and for development of pups was established as 160 mg/kg body weight/day. The value was established on the basis decreased number of pups per litter, decreased number of corpora lutea, decreased number of implantations, decreased fertility index in males and females and gestation index. In males no effect on reproduction was observed.

 

Based on the similarity in structure and manufacturing process, Solvent Red 19T would be expected to have the same properties, and the same NOAEL. (160mg/kg).

Effects on developmental toxicity

Description of key information

Read Across approach used to analogue substance. Assumption that target substance will have the same properties. Available data fro the source subtance Solvent Red 19E:

Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, oral (gavage), rat (Wistar Han) M/F, OECD guideline 422, GLP: NOAEL = 160 mg/kg bw/day

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
160 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is GLP compliant and has Klimisch score 1. The quality of the database is therefore considered to be good.
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

A read across approach was used to predict the reproductive toxicity properties of Solvent Red 19T ( 1-({2-methyl-4-[(2-methylphenyl)diazenyl]phenyl}diazenyl)-N-tridecylnaphthalen-2-amine).

The analogue source substance was Solvent Red 19E, which has the same structure, but where the tridecyl group has been replaced with a 2 -ethyl hexyl group. This material was assessed for reproductive toxicity according to guideline OECD 422. Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.

Wistar rats were dosed at 160, 400, 1000 mg/kg of body weight /day of Solvent Red 19E.

Reproduction

The course of mating, pregnancy and lactation of parental animals, weights of reproductive organs and pituitary gland, spermatogenesis and sperm parameters, microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation, post­ implantation and post-natal losses of mothers and number, weight, sex ratio and development of pups were not adversely affected by the test substance treatment at the lowest dose level. The number of females achieving pregnancy, total number of pups, mean weight of litters and fertility index were slightly decreased.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of prostate gland in males and ovaries, vagina, mammary gland and uterus in females were detected at the dose level 160 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

The course of mating, pregnancy and lactation, weights of reproductive organs, spermatogenesis, microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation losses of mothers and pathological examination of pups were not adversely influenced by the test substance treatment at the dose level 400 and 1000 mg/kg/day.

The number of females achieving pregnancy was decreased at the middle dose level. Calculation of reproduction parameters (significantly decreased number of corpora lutea and decreased number of uterus implantations) and fertility parameters (decreased fertility and gestation index) in animals showed mild changes at the middle dose level.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of prostate gland in males and ovaries, vagina and uterus in females were detected at the dose level 400 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

The number of females achieving pregnancy was decreased at the highest dose level. Examination of number and weight of pups (decrease of mean number of pups per litter and significant decrease of mean weight of litters), calculation of fertility parameters (decreased fertility index) in animals found out changes at the highest dose level.

Occurrence of macroscopic changes in females (red colouring of ovaries in females) and microscopic changes of ovaries, vagina and uterus in females were detected at the dose level 1000 mg/kg/day. These microscopic changes in reproductive organs did not relate to the test substance treatment.

 

The test substance administration had no adverse effect on mortality, growth of animals and some reproduction parameters - course of mating, pregnancy and lactation, spermatogenesis and microscopic structure of reproductive organs and pituitary gland of parental animals, number of pre-implantation losses of mothers and pathological examination of pups.

 

The test substance treatment affected the number of pups (decrease of mean number of pups and mean weight of litters, decreased number of corpora lutea and uterus implantations). The mean weight of pups was unchanged.

 

The value of NOAEL (No Observed Adverse Effect Level) for the reproduction and for development of pups was established as 160 mg/kg body weight/day. The value was established on the basis decreased number of pups per litter, decreased number of corpora lutea, decreased number of implantations, decreased fertility index in males and females and gestation index. In males no effect on reproduction was observed.

 

Based on the similarity in structure and manufacturing process, Solvent Red 19T would be expected to have the same properties, and the same NOAEL. (160mg/kg).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to reproductionand developmental toxicity.