Aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex

Endpoint summary

Description of key information

Repeated oral

The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.

Repeated Inhalation:

The short term toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical[The estimated vapor pressure of the test chemical was 3.86*10-21 Pa]. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal:

The acute dermal median lethal dose (LD50) of test chemical was considered to be >2000 mg/kg body weight. The test chemical did not cause any dermal reactions to humans and rats in the skin sensitization as well skin irritation studies respectively. Hence, it can be expected that the test chemical shall not exhibit 28 day repeated dose toxicity via dermal route. Hence, this endpoint was considered for waiver.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

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:

Weight of evidence approach based on various test chemicals

Justification for type of information:

Weight of evidence approach based on various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on various test chemicals

Principles of method if other than guideline:

Weight of evidence approach based on various test chemicals. The study 2,3 are referred as study 1,2

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: 1. Sprague Dawley; 2. Fischer 344

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

other: 1. Purina Laboratory Chow; 2. test substance contained in the diet

Details on oral exposure:

1. PREPARATION OF DOSING SOLUTIONS: The test material was incorporated into the basal diet using a Patterson-Kelley twin shell blender and used at dose levels of 0.0, 0.37, 1.39 and 5.19% (0, 180, 701, 2829 mg/kg bw/day males and 0, 228, 901, 3604 mg/kg bw/day for females)

DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diets were prepared and presented weekly.
- Mixing appropriate amounts with (Type of food): Purina
Laboratory Chow
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Purina Laboratory Chow
- Concentration in vehicle: 0.0, 0.37, 1.39 and 5.19% (0, 180, 701, 2829 mg/kg bw/day males and 0, 228, 901, 3604 mg/kg bw/day for females)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

2. PREPARATION OF DOSING SOLUTIONS: Not applicable
DIET PREPARATION
- Rate of preparation of diet (frequency):ones in 4 days
- Mixing appropriate amounts with (Type of food): Purina Laboratory Chow animal meal
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water): Not available
- Concentration in vehicle: Not available
- Amount of vehicle (if gavage): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

2. The stability of diets formulated with 100,000 ppm dye was determined by analyses performed after storage for 2 weeks at -20 , 5 , 25 , or 45 degree C. Spectrophotometric analysis of water extracts of
the diets indicated that the test chemical was stable in feed for 2 weeks at temperatures up to 45 degree C

Duration of treatment / exposure:

1. Males: 118 weeks
Females: 121 weeks
2. 103 weeks

Frequency of treatment:

1. 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods
2. daily

Remarks:

Males: 0.0, 0.37, 1.39 and 5.19% (0, 180, 701, 2829 mg/kg bw/day)
Females: 0.0, 0.37, 1.39 and 5.19% (0, 228, 901, 3604 mg/kg bw/day

Remarks:

Doses / Concentrations:
0,1250 mg/kg,2500 mg/kg

No. of animals per sex per dose:

1. 30/sex/group
2. Control-90 male and 90 female
1250 mg/kg-50 male and 50 female
2500 mg/kg-50 male and 50 female

Control animals:

yes, concurrent vehicle

Details on study design:

1. The dietary concentrations for this study were selected based on the results of previous subchronic studies in rats
2. - Dose selection rationale: Dose selected on the basis of Range-Finding and 14-Day Repeated Dose Studies and Subchronic Studies.
Range-Finding and 14-Day Repeated Dose Studies: In the single day dosing study, groups of five males and females of each rats were fed diets containing 6,000, 12,500, 25,000, 50,000, 100,000, or 200,000 ppm of the test chemical for 24 hours and then lab chow for 13 days. In the repeated dose study, similar groups of rats were fed diets containing 6,000, 12,500, 25,000, 50,000 or 100,000 ppm of the test chemical for 2 weeks. No deaths occurred among the rats in either study.
The low and high dietary levels of the test chemical selected for the chronic study with rats were 12,500 and 25,000 ppm.
- Rationale for animal assignment (if not random):Not available
- Rationale for selecting satellite groups: Not available
- Post-exposure recovery period in satellite groups: Not available
- Section schedule rationale (if not random): Not available

Observations and examinations performed and frequency:

1. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: gross signs of toxicity, death and morbidity were recorded daily. The rats were observed twice daily (5 days/wk) during the last 6 months of the study to minimize the loss of tissue to autolysis in rats that died on test.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly for wk 0 10, bi-weekly for wk 12-26, and every 4 wk thereafter

BODY WEIGHT: Yes
- Time schedule for examinations: weekly for wk 0 10, bi-weekly for wk 12 26, and every 4 wk thereafter

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):Yes weekly for wk 0 10, bi-weekly for wk 12 26, and every 4 wk thereafter

FOOD EFFICIENCY: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples were obtained from the tail vein during the study, and from the abdominal aorta at termination test were conducted at wk 13, 26, 52 and 78 and at termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: five rats/sex/group
- Parameters checked : haematocrit, haemoglobin, erythrocyte count, and total and differential leucocyte counts.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples were obtained from the tail vein during the study, and from the abdominal aorta at termination and clinical chemistry studies were performed on at week 52 and at termination
- Animals fasted: No data
- How many animals: 5 rats/sex/group
- Parameters checked: aspartate aminotransferase, Alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, fasting glucose, total protein, sodium, potassium, chloride, carbon dioxide (termination only) and serum electrophoresis

URINALYSIS: Yes
- Time schedule for collection of urine: Urine samples were obtained by housing rats overnight in individual metabolism cages. Urinary analysis was conducted at wk 13, 26, 52, 78 and at termination
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters checked : specific gravity, pH, glucose, ketones, total protein, bilirubin and sediment.

NEUROBEHAVIOURAL EXAMINATION: No data

OTHER:

2. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations : observations of sick, tumorbearing, and moribund animals were recorded
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Each month
BODY WEIGHT: Yes
- Time schedule for examinations:Monthly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY: No data
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: Not examined
- Time schedule for collection of blood: Not examined
- Anaesthetic used for blood collection: Not examined
- Animals fasted: Not examined
- How many animals: Not examined
- Parameters checked in table [No.?] were examined. Not examined

CLINICAL CHEMISTRY: Not examined
- Time schedule for collection of blood: Not examined
- Animals fasted: Not examined
- How many animals: Not examined
- Parameters checked in table [No.?] were examined. Not examined

URINALYSIS: No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined.: No data

NEUROBEHAVIOURAL EXAMINATION: Not examined
- Time schedule for examinations: Not examined
- Dose groups that were examined: Not examined
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not examined

Sacrifice and pathology:

1. GROSS PATHOLOGY: Yes
Gross autopsies were conducted on all rats that died spontaneously, were killed in a moribund condition, or were killed at the end of the study. Rats were killed by exsanguination under sodium pentobarbital. Absolute and relative organ weights were determined for the heart, liver, spleen, kidneys, testes with epididymides, and thyroid and adrenal glands.


HISTOPATHOLOGY: Yes
Complete histology was conducted on all rats from the control and high-dose groups. The following tissues from these rats were examined histologically: brain, pituitary, thoracic spinal cord, eyes, oesophagus, thyroid, thymus, heart, lungs, liver, spleen, pancreas, stomach, small and large intestine, mesenteric lymph node, kidneys, adrenal, urinary bladder, uterus, prostate, ovaries, testes with epididymides, seminal vesicles, skin, rib junction, bone marrow, nerve with muscle, and any tissue masses or lesions. Histology was also conducted on animals from any group with grossly observed masses or lesions. If a potential effect was consistently noted in a tissue then that tissue was examined histologically in all rats. All excised tissues not exhausted for histology were preserved.

2. GROSS PATHOLOGY: Yes
Animals were killed using carbon dioxide and necropsied.
HISTOPATHOLOGY: Yes
Neoplastic and Non neoplastic lesions examined microscopically
The following tissues were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur) and thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, eye, and all tissue masses.

Statistics:

1. Gain in group mean body weight and total food consumption for weeks 0-54, group mean body weight at termination, and absolute and relative organ weights were analysed by the methods of Bartlett (1937), Snedecor and Cochran (1967) and Scheffe (1953). Survival data were analysed by the methods of Sachs (1959) and Snedecor and Cochran (1967). Tumour incidence data were analysed by the methods described by Thomas et al. (1977). All analyses were considered
significant at P <0.05. Time-to-tumour analyses were not performed because data correlating the time of tumour development to the time of death were not
generated.
2.
1.Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier.
2. Possible dose-related effect on survival- method of Cox
3. Dose-related trend- Tarone's extensions of Cox's.
4.P values less than 0.05
5. Comparition of the tumor incidence One-tailed Fisher exact test.
6. For linear trend in proportions, with continuity correction- Cochran-Armitage test.

Clinical signs:

no effects observed

Description (incidence and severity):

1. Localized hair loss (apparently due to friction against the cage) and nasal and ocular discharge occurred at low incidences throughout the study in control and treated rats. A red tint to the fur was noted in treated rats, and the faeces of mid- and high-dose rats were red. Palpable masses were noted with equal incidences in the control and treated groups.

Mortality:

no mortality observed

Description (incidence):

1. There were no compound-related effects on survival
2. The survival of male and female rats was similar between treated animals and controls (males: control 70/90 (78%); low dose 36/50 (72%); and high dose 38/50 (76%) and females: control 66/88 (75%); low dose 40/50 (80%) and high dose 37/50 (74%)).

Body weight and weight changes:

no effects observed

Description (incidence and severity):

1. Group mean body weights at the end of the study were decreased in rats that received FD & C Red No. 40 except for the mid-dose 701 mg/Kg bw/day males, in which they were increased.The mean body weight of the high-dose 3604 mg/Kg bw/day females at the end of the study was significantly less than that of the controls.
2. The mean body weights of male rats administered the high dose were slightly lower than the control animals throughout the study.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

1. Food consumption were increased in 2829 mg/Kg bw/day foe males and 3604 mg/Kg bw/day for females in the treated group but not significantly so as compared to control

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

1. Few of the hematological differed significantly between control and treated rats, and none of the differences were compound related.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

1. Few of the Clinical chemistry differed significantly between control and treated rats, and none of the differences were compound related.

Urinalysis findings:

no effects observed

Description (incidence and severity):

1. Few of the urinanalysis differed significantly between control and treated rats, and none of the differences were compound related.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

1. No compound-related changes in organ weights, were noted in rats that died on test or that were killed in a moribund state or at the end of the study.

Gross pathological findings:

no effects observed

Description (incidence and severity):

1. No compound related adverse effect observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

1. Histological evaluation revealed a variety of lesions, including neoplasm, among the control and treated rats.
The lesions were present at similar incidences in control and treated rats and appeared to be spontaneous. None of the lesions were determined to be related to the administration of the test chemical
2. Histopathological examination revealed no evidence of carcinogenicity related to treatment with the test material. No other effects were reported.No compound-related neoplastic or non-neoplastic lesions were observed in the rats

Histopathological findings: neoplastic:

not specified

Description (incidence and severity):

2. No compound-related neoplastic or non-neoplastic lesions were observed in the rats

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

> 900 - <= 1 250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

gross pathology

mortality

organ weights and organ / body weight ratios

Remarks on result:

other: not specified

Critical effects observed:

not specified

Conclusions:

The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.

Executive summary:

Repeated oral

Data available from different studies were reviewed to determine the repeated dose oral toxicity of test chemical. The studies are as mentioned below:

Study 1:

Combined repeated dose and carcinogenicity study was performed on Sprague Dawley rats to determine its toxicity.

30 Sprague Dawley rats per sex per dose group were fed the test chemical in diet at dose concentration of 0, 0.37, 1.39 or 5.19% (0, 180, 701, 2829 mg/kg bw/day for males and 0, 228, 901, 3604 mg/kg bw/day for females), 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods. The animals were observed for clinical signs, mortality, morbidity, body weight and food consumption changes, hematology, clinical chemistry, gross and histopathology.

No significant compound related adverse effect were observed on mortality, clinical signs, body weight (except for a reduction in body weight in high-dose 3604 mg/Kg bw/day females at the end of the study), food consumption, hematology, clinical chemistry, gross and histopathology.

The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.

Study 2:

A combined repeated dose toxicity and carcinogenesis study was conducted using groups of 50 male and 50 female F344 rats which were fed diets containing 1250 or 2500 mg/kgbw/day of the test chemical for 103 weeks. Groups of 90 male and 90 female rats served as undosed controls.

The doses for the study were decided on the basis of a single day and sub chronic dose studies.In the single day dosing study, groups of five males and females of each rats were fed diets containing 6,000, 12,500, 25,000, 50,000, 100,000, or 200,000 ppm of the test chemical for 24 hours and then lab chow for 13 days. In the repeated dose study, similar groups of rats were fed diets containing 6,000, 12,500, 25,000, 50,000 or 100,000 ppm of the test chemical for 2 weeks. No deaths occurred among the rats in either study.

Based on the single dose and subchronic study, 0,1250 mg/kg,2500 mg/kg were the concentrations of the test and control groups when dosed with the test chemical for 103 weeks. All animals were observed twice daily, and observations of sick, tumorbearing, and moribund animals were recorded. Clinical examination and palpation for masses were performed each month, and the animals were weighed at least monthly. Gross and microscopic examinations were performed on major tissues, major organs, and all gross lesions from killed animals and from animals found dead. The tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The following tissues were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur) and thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, eye, and all tissue masses. Necropsies were performed on all animals found dead, unless precluded in whole or in part by autolysis or cannibalization. Thus, the number of animals from which particular organs or tissues were examined microscopically varies and does not necessarily represent the number of animals that were placed on study in each group.

Throughout the study, mean body weights of high-dose female rats and all low-dose groups were comparable with those of the controls, but mean body weights of high-dose male rats were slightly lower (10% or less) than those of the controls. The survival of male and female rats was similar between treated animals and controls (males: control 70/90 (78%); low dose 36/50 (72%); and high dose 38/50 (76%) and females: control 66/88 (75%); low dose 40/50 (80%) and high dose 37/50 (74%)). The mean body weights of male rats administered the high dose were slightly lower than the control animals throughout the study. No compound-related neoplastic or non-neoplastic lesions were observed in the rats.

Therefore, the No Observed Effect level[ NOAEL] was considered to be 1250 mg/kg and 2500 mg/kg for males and females, respectively, based on the effects observed on mean body weight, survival rate and histopathology.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

900 mg/kg bw/day

Study duration:

chronic

Experimental exposure time per week (hours/week):

168

Species:

rat

Quality of whole database:

Klimisch Rating 2- data is from peer reviewed journals

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Additional information

Repeated oral

Data available from different studies were reviewed to determine the repeated dose oral toxicity of test chemical. The studies are as mentioned below:

Study 1:

Combined repeated dose and carcinogenicity study was performed on Sprague Dawley rats to determine its toxicity.

30 Sprague Dawley rats per sex per dose group were fed the test chemical in diet at dose concentration of 0, 0.37, 1.39 or 5.19% (0, 180, 701, 2829 mg/kg bw/day for males and 0, 228, 901, 3604 mg/kg bw/day for females), 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods. The animals were observed for clinical signs, mortality, morbidity, body weight and food consumption changes, hematology, clinical chemistry, gross and histopathology.

No significant compound related adverse effect were observed on mortality, clinical signs, body weight (except for a reduction in body weight in high-dose 3604 mg/Kg bw/day females at the end of the study), food consumption, hematology, clinical chemistry, gross and histopathology.

The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.

Study 2:

A combined repeated dose toxicity and carcinogenesis study was conducted using groups of 50 male and 50 female F344 rats which were fed diets containing 1250 or 2500 mg/kgbw/day of the test chemical for 103 weeks. Groups of 90 male and 90 female rats served as undosed controls.

The doses for the study were decided on the basis of a single day and sub chronic dose studies.In the single day dosing study, groups of five males and females of each rats were fed diets containing 6,000, 12,500, 25,000, 50,000, 100,000, or 200,000 ppm of the test chemical for 24 hours and then lab chow for 13 days. In the repeated dose study, similar groups of rats were fed diets containing 6,000, 12,500, 25,000, 50,000 or 100,000 ppm of the test chemical for 2 weeks. No deaths occurred among the rats in either study.

Based on the single dose and subchronic study, 0,1250 mg/kg,2500 mg/kg were the concentrations of the test and control groups when dosed with the test chemical for 103 weeks. All animals were observed twice daily, and observations of sick, tumorbearing, and moribund animals were recorded. Clinical examination and palpation for masses were performed each month, and the animals were weighed at least monthly. Gross and microscopic examinations were performed on major tissues, major organs, and all gross lesions from killed animals and from animals found dead. The tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The following tissues were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur) and thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, eye, and all tissue masses. Necropsies were performed on all animals found dead, unless precluded in whole or in part by autolysis or cannibalization. Thus, the number of animals from which particular organs or tissues were examined microscopically varies and does not necessarily represent the number of animals that were placed on study in each group.

Throughout the study, mean body weights of high-dose female rats and all low-dose groups were comparable with those of the controls, but mean body weights of high-dose male rats were slightly lower (10% or less) than those of the controls. The survival of male and female rats was similar between treated animals and controls (males: control 70/90 (78%); low dose 36/50 (72%); and high dose 38/50 (76%) and females: control 66/88 (75%); low dose 40/50 (80%) and high dose 37/50 (74%)). The mean body weights of male rats administered the high dose were slightly lower than the control animals throughout the study. No compound-related neoplastic or non-neoplastic lesions were observed in the rats.

Therefore, the No Observed Effect level[ NOAEL] was considered to be 1250 mg/kg and 2500 mg/kg for males and females, respectively, based on the effects observed on mean body weight, survival rate and histopathology.

Repeated Dose Inhalation

The short term toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical[The estimated vapor pressure of the test chemical was 3.86*10-21 Pa]. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal

The acute dermal median lethal dose (LD50) of test chemical was considered to be >2000 mg/kg body weight. The test chemical did not cause any dermal reactions to humans and rats in the skin sensitization as well skin irritation studies respectively. Hence, it can be expected that the test chemical shall not exhibit 28 day repeated dose toxicity via dermal route. Hence, this endpoint was considered for waiver.

Justification for classification or non-classification

Based on the available studies, the test chemical can be considered to be not toxic when exposed repeated via oral route. Hence, it can be classified under the category "Not Classified" as per CLP Regulation.