Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive toxicity study

The data available for Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates) and structurally similar read across chemicals was reviewed to determine the reproductive toxicity .The NOAEL for reproductive toxicity was considered to be above 250 - 375mg/kg bw/day as no effects on reproductive parameters  .When male and female rats or mice were treated withReaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates. Thus, comparing this value with the criteria of CLP regulation Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates not likely to classify as reproductive toxicant.

 

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data of read across substances

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

WoE report is based on two reproductive toxicity studies on rats 1.Reproductive and developmental toxicity study of test material was performed on Sprague Dawley rats. 2.The carcinogenic & reproductive effect in test material on F344/N rats were assessed in a parental generation.3.The carcinogenic & reproductive effect of test material in B6C3F1 mice were assessed in a parental generation

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Species:

other: 1 & 2 .rats 3.mice

Strain:

other: 1.Sprague-Dawley 2.Fischer 344 3.B6C3F1

Details on species / strain selection:

No data available

Sex:

female

Details on test animals or test system and environmental conditions:

Study 1.Details on test animals and env. conditionsTEST ANIMALS- Source: Charles River Breeding Laboratories. Inc. Shaver Road Portage. Michigan 49081- Age at study initiation: female: Six weeks ,male : Seven weeks- Weight at study initiation: mean: 207grams(167.6-311.1g)- Fasting period before study:- Housing: Individually. except during the first week of the acclimation period (two females/cage) and mating. in stainless steel suspended cages with wire mesh floors.- Use of restrainers for preventing ingestion (if dermal): yes/no- Diet (e.g. ad libitum): Purina. Certified Rodent Chow No. 5002 (mash) fed ad libitum.- Water (e.g. ad libitum): Tap water delivered by automatic watering system, ad libitum (Elizabethtown Water Company).- Acclimation period:21 days ENVIRONMENTAL CONDITIONS- Temperature (°C):18.88-23.33°C- Humidity (%):26-68%- Air changes (per hr):- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle (7 AM to 7 PM) via automatic timerStudy 2TEST ANIMALS- Source: Charles River Breeding Laboratories - Age at study initiation: 7-8 weeks- Weight at study initiation: NA- Fasting period before study: NA- Method of Animal Identification: Ear tag- Housing: 5 animals per cage- Cages: Polycarbonate (Lab Products, Inc., Rochelle Park, NJ, or Hazleton Systems, Inc., Aberdeen, MD)- Cage Filters: Spun-bonded polyester, Dupont 2024® (Snow Filtration, Cincinnati, OH)- Bedding: Hardwood chips (P.J. Murphy Forest Products Corp., Rochelle Park, NJ)- Diet (e.g. ad libitum): NIH 07 Rat Ration, available ad libitum- Water (e.g. ad libitum): Automatic watering system, available ad libitum- Acclimation period: 19 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18.88°-30° C- Humidity (%):22% - 80%;- Air changes (per hr): 12-15 room air changes/h- Photoperiod (hrs dark / hrs light): Fluorescent light 12 h/dStudy 3TEST ANIMALS- Source: Charles River Breeding Laboratories- Age at study initiation: 9-10 wk- Weight at study initiation: No Data- Fasting period before study:No Data- Housing: Five animals per cage- Cage: Polycarbonate (Lab Products, Inc., Rochelle Park, NJ, or Hazleton Systems, Inc., Aberdeen, MD)- Cage Filterds: Spun-bonded polyester, Dupont 2024® (Snow Filtration, Cincinnati, OH)- Bedding: Hardwood chips (P.J. Murphy Forest Products Corp., Rochelle Park, NJ)- Diet (e.g. ad libitum): Mouse Ration; available ad libitum- Water: Automatic watering system, ad libitum- Acclimation period: 26 days ENVIRONMENTAL CONDITIONS- Temperature : 18.88 -30° C- Humidity (%): 22%-80%;- Air changes (per hr): 12-15 room air changes/h- Photoperiod (hrs dark / hrs light): fluorescent light 12h/d

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Study 1.Details on exposurePREPARATION OF DOSING SOLUTIONS:Test material dissolved in corn oil DIET PREPARATION- Rate of preparation of diet (frequency):No data available- Mixing appropriate amounts with (Type of food )- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): corn oil - Concentration in vehicle: 0, 50,250,500mg/kg bw/day- Amount of vehicle (if gavage): 5ml/kg bw/day - Lot/batch no. (if required): No data available- Purity: No data availableStudy 2&3Details on oral exposurePREPARATION OF DOSING SOLUTIONS:Test substance was diluted in cotton-seed oil in a concentration sufficient to provide the predetermined dosage in 2% of the diet. The oil solutions were incorporated into a nutritionally adequate basal ration (Purina Laboratory Chow).Dosages were administered on a uniform body weight basis by biweekly adjustments of the concentration of the test material in the cotton-seed oil.DIET PREPARATION- Rate of preparation of diet (frequency): - Mixing appropriate amounts with (Type of food): - Storage temperature of food: 5°C- Maximum Storage Time: 3 weeksOther:test material was stable as a bulk chemical when stored protected from light for 2 weeks at temperatures up to 60° C. Dose mixtures were stored no longer than 3 weeks at 5° C for the 2-year studies.

Details on mating procedure:

Study1.Mated females were used

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Study 2&3During the 2-year studies, the dose mixtures were analyzed at approximately 8-week intervals. For the studies, dose analyses were conducted 13-15 times at 1to 2-month intervals throughout the studies and all the mixtures were formulated within ± 10% of the target concentrations. Results of periodic referee analysis performed by the analytical chemistry laboratory indicated good agreement with the results from the study laboratory.

Duration of treatment / exposure:

Study1.10 days ( from day 6 through day 15 of gestation )Study 2&3Two years (103 weeks)

Frequency of treatment:

Study 1.dailyStudy 2&3.5 d/wk for 103 wk

Details on study schedule:

No data available

Remarks:

Study1.0, 50,250,500 mg/kg bw/dayStudy 2&30, 375, or 750 mg/kg

No. of animals per sex per dose:

Study1.Total:1010 mg/kg bw/day:2450mg/kg bw/day:24250mg/kg bw/day:24500 mg/kg bw/day:29Study 2&3Total :300Control: 50 males and 50 females375 mg/kg: 50 males and 50 females750 mg/kg: 50 males and 50 females

Control animals:

yes, concurrent vehicle

Details on study design:

Study 2&3- Dose selection rationale: Because there were no deaths or life-threatening histopathologic lesions attributed to test material at 375 or 750 mg/kg, these doses were selected for male and female rats for the 2-year studies, administered in corn oil by gavage, 5 days per week.- Rationale for animal assignment: Animals distributed to weight classes and then assigned to cages and to groups by a table of random numbers

Positive control:

No data available

Parental animals: Observations and examinations:

Study1.Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Twice daily (morning and afternoon) for signs of pharmacologic or toxicologic effects and mortality. In addition. eachfemale was given a detailed physical examination on Days 0. 10. 12. 15 and 20 of gestation. On Days 6. 10. 12 and 15 of gestation the examinations were given after dosing. Time schedule: twice daily BODY WEIGHT: YesTime schedule for examinations: Recorded on Days 0. 6. 10. 12, 15 and 20 of gestation.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Recorded for the following intervals during gestation: Days 0 to 5. 6 to 10. 10 to 15 and 15 to 20. Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations: OTHER: Study 2&3.All rats were observed for viability at least twice daily throughout the study.Observations were also made for clinical signs of the effects of chemical

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

Study1.All fetuses were given a gross examination for external malformations/variations to include observation for palatal defects. Subsequently. Each fetus was weighed and individually identified. The sex of each fetus was noted externally (ano-genital distance) and was confirmed by internal inspection of the gonads at subseqaent evaluation

Postmortem examinations (parental animals):

Study1.Postmortem examinations (Parent Animal)SACRIFICE: Day 20 of gestation using Lethal exposure to ether.GROSS NECROPSY: Complete gross postmortem examinations were performed on all mated females including those dying spontaneously or sacrificed in a moribund condition. External surface, all orifices, thecranial cavity, carcass, the external surface of the spinal cord and sectioned surfaces of the brain, nasal cavity and paranasal sinuses, the thoracic, abdominal and pelvic cavities and their viscera and the cervical tissues and organs were examined for all animals. The carcass of each female was discarded at the completion of the gross post-mortem evaluationHISTOPATHOLOGY / ORGAN WEIGHTSThe tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively. macroscopic examination was performed .Study 2&3Animals found moribund and those surviving to the end of the studies were humanely killed.GROSS PATHOLOGY: Yes

Postmortem examinations (offspring):

Study1.Postmortem examinations (offspring)SACRIFICEApproximately one-half of the fetuses in each litter (alternating fetuses within the litter) were evaluated for soft tissue malformations/variations

Statistics:

Study 2&3Life Table Analyses:This method of analysis assumed that all tumors of a given type observed in animals dying before the end of the study were fatal; i.e., they either directly or indirectly caused the death of the animal. According to this approach, the proportions of tumor-bearing animals in the dosed and vehicle control groups were compared at each point in time at which an animal died with a tumor of interest. The denominators of these proportions were the total number of animals at risk in each group. These results, including the data from animals killed at the end of the study, were then combined by the Mantel-Haenszel method (1959) to obtain an overall P value. This method of adjusting for intercurrent mortality is the life table method of Cox and of Tarone.Incidental Tumor Analyses:This method of analysis assumed that all tumors of a given type observed in animals that died before the end of the study were incidental; i.e., they were merely observed at necropsy in animals dying of an unrelated cause. According to this approach, the proportions of tumor-bearing animals in dosed and vehicle control groups were compared in each of five time intervals: weeks 0-52, weeks 53-78, weeks 79-92, week 93 to the week before the terminal-kill period, and the terminal-kill period. The denominators of these proportions were the number of animals actually examined for tumors during the time interval. The individual time interval comparisons were then combined by the previously described method to obtain a single overall result.Fisher Exact/Cochran-Armitage Trend Analyses:In addition to survival-adjusted methods, the results of the Fisher exact test for pairwise comparisons and the Cochran-Armitage linear trend test are given in the appendixes containing the analyses of tumor incidence. These two tests are based on the overall proportion of tumor-bearing animals and do not adjust for survival differences.

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Study1.In the 50mg/kg bw dose group three females were noted with excessive salivation during the physical evaluations. No other adverse effects of treatment at this dose level were noted from the physical evaluations.Rats in the 250mg/kg and 500mg/kg dose groups also had excessive lacrimation and staining of the skin/fur in the ano-genital region

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

Study1.No mortality occurred in the control. 50mg/kg and 250mg/kg dose groups. In the 500mg/kg dose group two females died and three females were sacrificed in a moribund condition (17.2 %mortality rate).

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Study1.In the 50mg/kg bw dose group mean weight gains for the Day 6-15 treatment interval of gestation and for the Day 6-20 gestation interval using corrected Day 20 weights were lower than control (-14.3 %and -12.1%, respectively); however, these differences from control data were not statistically significant. In the 250mg/kg dose group. Mean weight gains for the Day 6-15 and 6-20 gestation intervals were lower than control (-19.0% and -16.4%, respectively); however, only for the Day 6-15 gestation interval did these data differ statistically from control data. In the 500mg/kg dose group mean weight gain data for the Day 6-15 and 6-20 gestation intervals were markedly lower than control (--71.4 % and- 56.8%, respectively) and these data differed statistically from control data.Study 2.Body weights were 20%-30% below those of vehicle controls in high dose male and female rats at study termination.In the low dose groups, body weight reduction occurred only in male rats during the last 10 weeks of the studyStudy 3.body weight in 750mg/kg dose group lower than vehicle controls

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Study1.During the treatment period mean food consumption was lower than control in each of the treated groups. In the low-dose group, mean food consumption was significantly lower than control during the Day 6-10 gestation interval (-12.1%) but was comparable to control for the day 10-15 intervals. In the mid-dose group. Mean food consumption was significantly lower than control during both the Day 6-10 and 10-15 gestation intervals (-22.0% and -11.7%. respectively). Similarly, in the high-dose group. mean food consumption was significantly lower than control during both the Day 6-10 and 10-15 gestation intervals (-47.3% and -13.8%. respectively).

Food efficiency:

effects observed, treatment-related

Description (incidence and severity):

food consumption in 750mg/kg dose group lower than vehicle controls

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

Study1.The pregnancy rate was 100% in 50mg/kg bw dose group. 95.8% (23/24 females) in the control and 250mg/kg bw dose groups and 96.6% (28/29 females) in the 500mg/kg bw dose group. No adverse effect of treatment was evident from pregnancy rate data.The mean number of corpora lutea and uterine implantations was considered comparable between the control and treated groups.The mean number of resorption sites per pregnant female was comparable between the controls. 50mg/kg bw and 250mg/kg bw dose groups. In the 500mg/kg bw dose group, the mean number of resorption sites was higher than control; however, this difference was not statistically significant.

Dose descriptor:

NOAEL

Effect level:

> 250 - <= 375 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

reproductive performance

Remarks on result:

other: No effects on reproductive performance

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Description (incidence and severity):

Study1.The mean number of viable fetuses per pregnant female was comparable between the control and treated groups

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Study1.mean fetal weight unaffected at 50mg/kg bw and 250mg/kg bw dose mean fetal weight statistically lower than control

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

Study1.Evaluation of fetuses recovered from treated group females for external, visceral and skeletal malformations indicated no adverse effect of treatment. At the 500mg/kg bw dose level, the incidence of fetuses with unossified sternebral elements (particularly the fifth and sixth sternebrae) was increased suggestive of a retardation in ossification.

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

mortality

body weight and weight gain

gross pathology

Remarks on result:

other: overall no developmental toxic effects observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 250mg/kg bw .When female Sprague Dawley rats were treated with Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates orally.

Executive summary:

Data available from different studies were reviewed to determine thereproductive toxicityReaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates. The studies are as mentioned below:

Study1.

The reproductive and developmental toxicity study of test material was performed on mated female Sprague Dawley rats according EPA OTS 798.4900. The test material dissolved in corn oil and administered in dose concentration0, 50,250,500 mg/kg bw/day by oral gavage route from day 6 to 15 of gestation in dose volume 5ml/kg bw .The control, 50mg/kg and 250 mg/kg dose groups contained 24 females each; the 500mg/kg dose group contained a total of 29 females. All the animals were observedtwice daily for signs of pharmacologic or toxicologic effects and mortality. In addition, Each female was given a detailed physical examination on Days 0, 10,12, 15 and 20 of gestation. On Days 6, 10, 12 and 15 of gestation the examinations were given after dosing. Body weight recorded on Days 0, 6, 10,12, 15 and 20 of gestation. Food Consumption recorded for the following intervals during gestation Days 0 to 5, 6 to 10 ,10 to 15 and 15 to 20. Females were sacrificed on Day 20 of gestation and given a gross postmortem examination. Ovaries were evaluated for number of corpora lutea and uterine implantation data were evaluated for number of live, dead and resorbed fetuses. Fetuses recovered at this time were weighed,sexed and evaluated for external malformations; approximately one-half of the fetuses in each litter (alternating fetuses Within the litter) were processed for soft tissue examination (micro dissection procedure) and the remaining fetuses were processed for skeletal evaluations (Alizarin Red S).

Some maternal toxicity was evident at each dose level. 50mg/kg bw dose group females experienced depressed weight gain during the treatment period; however, these data did not differ statistically from control. Mean food consumption for the Day 6-10 interval of treatment in the 50mg/kg bw dose group was statistically lower than control and three 50mg/kg bw dose females experienced excessive salivation during the treatment period. Similar manifestations of maternal toxicity were seen at the 250mg/kg bw and 500mg/kg bw dose levels; however, the effects were more extreme. Physical examination of females in the 250mg/kg bw and 500mg/kg bwdosegroups revealed an increased incidence of females with excessive salivation, staining of the skin/fur in the ano-genital area and excessive lacrimation. At the 500mg/kg bw dose level, two females died and three females were sacrificed in a moribund condition (mortality rate:l7.2%)no mortality occurred in the 50mg/kg bw or 250mg/kg bw dose groups. No adverse effect of treatment was evident from uterine implantation Mean fetal weight and fetal sex distribution were unaffected by treatment at the 50mg/kg bw or 250mg/kg bw dose levels. In the 500mg/kg bw dose group, mean fetal weight data as a composite for both sexes and when distinguished by sex, were statistically lower than control. Evaluation of fetuses recovered from treated group females for external, visceral and skeletal malformations indicated no adverse effect of treatment. At the 500mg/kg bw dose level, the incidence of fetuses with unossified sternebral elements (particularly the fifth and sixth sternebrae) was increased suggestive of a retardation in ossification. HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 250mg/kg bw .When femaleSprague Dawley rats were treated withtest material orally.

Study 2.

A reproductive toxicity and carcinogenesis study of test material was conducted in F344/N rats.50 male & 50 female rats were orally administered with test material for two years at dose levels 375 or 750 mg/kg.No adverse effect observed on reproductive toxicity of incidence of neoplastic & non neoplastic lesion effect on male & female rats.Hence The No observed adverse effect level (NOAEL) was considered  to be 375 mg/kg.When male and female  F344/N rat was treated with test material orally.

Study 3

A reproductive toxicity and carcinogenesis study on 1-phenylethanol was conducted in B6C3F1 mice. 50 male & 50 female mice were orally administered with 1-phenylethanol for two years at dose levels 375 or 750 mg/kg. A reduction in body weight gain was apparent in the high dose groups of males and females. Final survival rates in mice were similar among groups (male: 39/49; 40/50; 28/50; female: 41/50; 41/50; 38/50). No neoplastic or non-neoplastic lesions were attributed to 1-phenylethanol administration in mice of either sex. The No observed adverse effect level (NOAEL) for reproductive toxicity in mice was found to be 375 mg/kg.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

subacute

Species:

other: rats or mice

Quality of whole database:

Data is Klimicsh 2 and from authoritative database

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity study

Data available from different studies were reviewed to determine the reproductive toxicity of Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates. The studies are as mentioned below:

Study1.

The reproductive and developmental toxicity study of test material was performed on mated female Sprague Dawley rats according EPA OTS 798.4900. The test material dissolved in corn oil and administered in dose concentration0, 50,250,500 mg/kg bw/day by oral gavage route from day 6 to 15 of gestation in dose volume 5ml/kg bw .The control, 50mg/kg and 250 mg/kg dose groups contained 24 females each; the 500mg/kg dose group contained a total of 29 females. All the animals were observed twice daily for signs of pharmacologic or toxicologic effects and mortality. In addition, Each female was given a detailed physical examination on Days 0, 10,12, 15 and 20 of gestation. On Days 6, 10, 12 and 15 of gestation the examinations were given after dosing. Body weight recorded on Days 0, 6, 10,12, 15 and 20 of gestation. Food Consumption recorded for the following intervals during gestation Days 0 to 5, 6 to 10 ,10 to 15 and 15 to 20. Females were sacrificed on Day 20 of gestation and given a gross postmortem examination. Ovaries were evaluated for number of corpora lutea and uterine implantation data were evaluated for number of live, dead and resorbed fetuses. Fetuses recovered at this time were weighed,sexed and evaluated for external malformations; approximately one-half of the fetuses in each litter (alternating fetuses Within the litter) were processed for soft tissue examination (micro dissection procedure) and the remaining fetuses were processed for skeletal evaluations (Alizarin Red S).

Some maternal toxicity was evident at each dose level. 50mg/kg bw dose group females experienced depressed weight gain during the treatment period; however, these data did not differ statistically from control. Mean food consumption for the Day 6-10 interval of treatment in the 50mg/kg bw dose group was statistically lower than control and three 50mg/kg bw dose females experienced excessive salivation during the treatment period. Similar manifestations of maternal toxicity were seen at the 250mg/kg bw and 500mg/kg bw dose levels; however, the effects were more extreme. Physical examination of females in the 250mg/kg bw and 500mg/kg bwdosegroups revealed an increased incidence of females with excessive salivation, staining of the skin/fur in the ano-genital area and excessive lacrimation. At the 500mg/kg bw dose level, two females died and three females were sacrificed in a moribund condition (mortality rate:l7.2%)no mortality occurred in the 50mg/kg bw or 250mg/kg bw dose groups. No adverse effect of treatment was evident from uterine implantation Mean fetal weight and fetal sex distribution were unaffected by treatment at the 50mg/kg bw or 250mg/kg bw dose levels. In the 500mg/kg bw dose group, mean fetal weight data as a composite for both sexes and when distinguished by sex, were statistically lower than control. Evaluation of fetuses recovered from treated group females for external, visceral and skeletal malformations indicated no adverse effect of treatment. At the 500mg/kg bw dose level, the incidence of fetuses with unossified sternebral elements (particularly the fifth and sixth sternebrae) was increased suggestive of a retardation in ossification. HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 250mg/kg bw .When femaleSprague Dawley rats were treated withtest material orally.

Study 2.

A reproductive toxicity and carcinogenesis study of test material was conducted in F344/N rats.50 male & 50 female rats were orally administered with test material for two years at dose levels 375 or 750 mg/kg.No adverse effect observed on reproductive toxicity of incidence of neoplastic & non neoplastic lesion effect on male & female rats.Hence The No observed adverse effect level (NOAEL) was considered  to be 375 mg/kg.When male and female  F344/N rat was treated with test material orally.

Study 3

A reproductive toxicity and carcinogenesis study on 1-phenylethanol was conducted in B6C3F1 mice. 50 male & 50 female mice were orally administered with 1-phenylethanol for two years at dose levels 375 or 750 mg/kg. A reduction in body weight gain was apparent in the high dose groups of males and females. Final survival rates in mice were similar among groups (male: 39/49; 40/50; 28/50; female: 41/50; 41/50; 38/50). No neoplastic or non-neoplastic lesions were attributed to 1-phenylethanol administration in mice of either sex. The No observed adverse effect level (NOAEL) for reproductive toxicity in mice was found to be 375 mg/kg.

Based on the data available from different studies, Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates did not showedreproductive toxicityat dose concentrationabove 250 - 375mg/kg bw/day.Hence the test chemical is not likely to classify as a reproductive toxicant as per the criteria mentioned in CLP regulation.

 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates not likely to classify as reproductive toxicant.