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EC number: 400-320-4 | CAS number: 94933-05-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
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- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
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- Solubility in organic solvents / fat solubility
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- Flash point
- Auto flammability
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- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
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- Nanomaterial aspect ratio / shape
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- Endpoint summary
- Stability
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- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- repeated dose toxicity: dermal, other
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From Sep. to Oct. 1983
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1984
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Version / remarks:
- 1981
- Deviations:
- yes
- Remarks:
- Females weighed less than protocol requirements. Temperature occasionally fell below 19 °C by 1 °C. Humidity occasionally exceeded upper limit.
- GLP compliance:
- not specified
- Limit test:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 400-320-4
- EC Name:
- -
- Cas Number:
- 94933-05-8
- Molecular formula:
- not applicable
- IUPAC Name:
- chromium(3+) trisodium bis(2-(2-{4-hydroxy-2-oxido-3-[2-(5-sulfonatonaphthalen-1-yl)diazen-1-yl]phenyl}diazen-1-yl)benzoate)
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Crl:CD(SD)BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Ltd., Manston Road, Margate, Kent, England
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: 148 to 245 g
- Housing: individually in stainless steel wire mesh cages (All Type Tools Ltd., Woolwich, England) suspended over cardboard-lined trays, replaced when necessary to maintain hygiene
- Diet: ad libitum except in periods of fasting before blood sampling; pelleted diet, SQC Rat and Mouse Maintenance Diet No. 1, Expanded (Special Diets Services Ltd., Stepfield, Witham, Essex, England) (tested for concentration of heavy metals, aflatoxins and insecticides)
- Water: ad libitum; mains water from glass bottles changed weekly and attached to cage (periodic analyses for heavy metals and chlorinated hydrocarbons supplied by local water authority; tested for polycyclic aromatic hydrocarbons)
- Acclimation period: 14 days after examination for external signs of good health
ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24 °C
- Humidity: 55 to 80 %
- Air changes: at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- water
- Remarks:
- distilled water
- Details on exposure:
- TEST SITE
- Area of exposure: dorso-lumbar region
- Coverage: 60 x 40 mm
- Applicaion: using a ball-ended metal cannula and a plastic disposable syringe.
- Type of wrap if used: porous gauze dressing then covered with a strip of impervious, non-irritating plastic wrapping (Sleek, Smith & Nephew, Welwyn Garden City, Herts, England); sealing ensured
- Time intervals for shavings or clipplings: as often as was necessary to maintain the area free of hair
REMOVAL OF TEST SUBSTANCE
- Washing: wiped, no washing
- Time after start of exposure: 6 hours
TEST MATERIAL
- Amount applied: 1000 mg/kg bw/day
- Concentration: 4.0 mg/kg bw/day
- Constant concentration used: yes
- Preparation: prepared daily before administration
USE OF RESTRAINERS FOR PREVENTING INGESTION: no - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 6 hours
- Frequency of treatment:
- daily for 28 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 1000 mg/kg bw/day: 5 males and 5 females
Control (distilled water without addition of test item): 5 males and 5 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: a limit test using a dose level of 1000 mg/kg bw/day was allocated because of a lack of observable toxic effects at dose levels up to 2000 mg/kg bw in an acute dermal toxicity study (report no. 3521-252/32).
- Rationale for animal assignment: the selected animals were classed according to body weights, and were then allocated to groups using a stratified randomisation based on body weight. - Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- MORBIDITY / MORTALITY
- Time schedule: daily. At the beginning and end of each working day all animals were examined to detect any which were dead or moribund
CLINICAL CONDITIONS
- Time schedule: each animal was given a detailed clinical examination once daily for signs of ill health or overt toxicity. An individual record of clinical changes observed was maintained for each animal
DERMAL IRRITATION
- Time schedule for examinations: daily
- The presence of any signs of cutaneous irritation to the application site was assessed daily before dosing. The cutaneous reaction to treatment was scored according to the Draize scale (1959), specified in Table 1: Draize sccores for skin irritation in "Any other information on materials and methods", below.
BODY WEIGHT
- Time schedule for examinations: individual body weights were recorded on the first day of test, at weekly intervals throughout the study and again on the day of necropsy
FOOD CONSUMPTION
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: yes
- Time schedule: the weight of food consumed individually by each animal was determined weekly
HAEMATOLOGY
- Time schedule for collection of blood: week 3
- Anaesthetic used for blood collection: yes, light anaesthesia (Diethyl ether, Analar grade, BDH, Poole, Dorset, England)
- Animals fasted: yes, 16 hours (overnight)
- How many animals: all (20)
- Procedure: parameters were measured on blood collected into tubes containing EDTA anticoagulant
- Parameters: see Table 2: Haematology parameters examined in "Any other information on materials and methods", below
CLINICAL CHEMISTRY
- Time schedule for collection of blood: week 3
- Animals fasted: yes, 16 hours (overnight)
- Anaesthetic used for blood collection: yes, light anaesthesia (Diethyl ether, Analar grade, BDH, Poole, Dorset, England)
- How many animals: all (20)
- Procedure: estimations were performed on plasma from blood collected into tubes containing lithium heparin anticoagulant.
- Parameters: see Table 3: Clinical chemistry parameters examined in "Any other information on materials and methods", below
FOOD EFFICIENCY: not monitored
WATER CONSUMPTION: not monitored
OPHTHALMOSCOPIC EXAMINATION: not monitored
URINALYSIS: not monitored
NEUROBEHAVIOURAL EXAMINATION: not monitored - Sacrifice and pathology:
- NECROPSY
The animals were killed by an intraperitoneal injection of pentobarbitone sodium solution (Euthatal, 200 mg/mL) (May & Baker, Dagenham, Essex, England) following an overnight fast. A full external and internal examination was made and all lesions were recorded.
GROSS PATHOLOGY
Organ weights were measured before fixation, while still wet, of adrenals, kidneys, liver and testes.
HISTOPATHOLOGY
Samples of the following tissues from all animals were preserved in 10 % neutral buffered formalin: adrenals, kidneys, gross lesions, liver, treated skin (2 sites), untreated skin (2 sites). The tissues were then embedded in paraffin wax B. P., sectioned at a nominal thickness of 5 µm and stained with haematoxylin and eosin. Microscopic evaluation: sections of tissue were examined by the study pathologist. - Statistics:
- Data were processed to give group mean values and standard deviations, where appropriate.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related clinical signs observed in either treatment or control animals.
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- - Test animals: slight redness of the treated skin site was noted in some females exposed to the test item on days 2 to 4 and in 1 male on days 23 to 28. Slightly increased redness (grade 2) was noted on the treated skin site on female 16 on days 22 to 29 and in female 20 on days 11 to 26. Very slight oedema was also noted on female 20 on days 11 and 12. One female showed skin sores on its back probably due to the occlusive dressing.
- Control animals: no adverse skin redness was noted in control animals. - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- - Test animals: no mortality was recorded in the 28-day study period.
- Control animals: one conrol male was found dead on day 22. - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Overall body weight gains during the treatment period were considered to be similar in all animals. No notable difference in body weight gain was observed between the test and control groups of animals.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No adverse effects on food intake observed among either test or control animals.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No changes in the haematologic parameters of treated animals that could be attributed to treatment with the test item.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No changes in the clinical chemistry parameters that could be attributed to treatment with the test item.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- All absolute organ weights and organ weight to body weight ratios were considered similar for treated and control animals.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - Test animals: brown discolouration on the tail, attributed to contamination by the test item; sores and fur loss on the abdomen, attributed to the adhesive bandage.
- Control animals: sores and fur loss on the abdomen, attributed to the adhesive bandage; one male died of a urinary tract obstruction which was considered an isolated and not study-related finding. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Skin reactions in the treated skin site of control rats consisted primarily of low grade acanthosis. This was more noticeable in males than females. The skin sites exposed to the test item were generally similar to those of the controls. One male and 1 female had erosions, but these were minor focal lesions, probably of traumatic origin, and the rest of the treated skin area was similar to controls. Overall, there was no evidence of any significant skin irritation due to repeated percutaneous application of the test item.
Histopathology findings in the selected tissues examined were generally infrequent and of minor nature such as hyaline droplets in the kidney of males and leukocyte foci in the livers of both sexes. There were no findings of any unusual nature or incidence to suggest any systemic toxic effect due to test item administration. - Histopathological findings: neoplastic:
- not specified
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- dermal irritation
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1: Mean body weight and standard deviation (S.D.)
Week of study | Group and gender | ||||
1M | 2M | 1F | 2F | ||
start | mean: | 221.6 | 218.8 | 158.8 | 156.6 |
S.D.: | 10.01 | 15.94 | 8.98 | 7.09 | |
1 | mean: | 265.4 | 264.4 | 175.0 | 174.4 |
S.D.: | 13.81 | 18.74 | 11.77 | 9.02 | |
2 | mean: | 301.0 | 303.2 | 191.0 | 191.0 |
S.D.: | 19.91 | 25.91 | 13.62 | 11.81 | |
3 | mean: | 311.5 | 319.4 | 200.2 | 194.2 |
S.D.: | 22.11 | 28.12 | 15.55 | 14.81 | |
4 | mean: | 339.3 | 340.2 | 210.6 | 206.8 |
S.D.: | 24.03 | 28.65 | 19.81 | 16.45 |
Table 2: Mean food consumption (g/week) and standard deviation (S.D.).
Week of study | Group and gender | ||||
1M | 2M | 1F | 2F | ||
1 | mean: | 230.4 | 201.2 | 159.8 | 193.2 |
S.D.: | 19.82 | 12.32 | 15.74 | 89.50 | |
2 | mean: | 218.4 | 213.2 | 158.0 | 155.8 |
S.D.: | 18.69 | 22.71 | 15.60 | 13.52 | |
3 | mean: | 200.2 | 212.4 | 170.2 | 149.8 |
S.D.: | 45.07 | 19.09 | 18.62 | 11.82 | |
4 | mean: | 236.5 | 219.2 | 176.8 | 163.2 |
S.D.: | 8.19 | 8.29 | 18.89 | 14.13 |
Table 3: Individual body weights (g).
Group number | Animal number | Body weights (g) at week: | ||||
0 | 1 | 2 | 3 | 4 | ||
1M | 1 | 216 | 266 | 313 | 329 | 350 |
2 | 234 | 268 | 297 | 305 | 333 | |
3 | 220 | 277 | 310 | - | - | |
4 | 229 | 274 | 317 | 329 | 365 | |
5 | 209 | 242 | 268 | 283 | 309 | |
2M | 6 | 213 | 268 | 313 | 336 | 354 |
7 | 205 | 245 | 278 | 290 | 303 | |
8 | 245 | 290 | 325 | 336 | 351 | |
9 | 222 | 272 | 327 | 347 | 374 | |
10 | 209 | 247 | 273 | 388 | 319 | |
1F | 11 | 168 | 187 | 209 | 211 | 222 |
12 | 148 | 164 | 183 | 190 | 199 | |
13 | 157 | 174 | 183 | 196 | 209 | |
14 | 168 | 187 | 202 | 221 | 237 | |
15 | 153 | 163 | 178 | 183 | 186 | |
2F | 16 | 153 | 180 | 199 | 205 | 222 |
17 | 152 | 175 | 191 | 190 | 209 | |
18 | 159 | 165 | 181 | 182 | 197 | |
19 | 151 | 166 | 178 | 180 | 184 | |
20 | 168 | 186 | 206 | 214 | 222 |
Table 4: Individual food consumption (g/week).
Group number | Animal number | Consumption (g) at week: | |||
1 | 2 | 3 | 4 | ||
1M | 1 | 243 | 247 | 235 | 247 |
2 | 233 | 206 | 212 | 230 | |
3 | 253 | 226 | 122 | - | |
4 | 221 | 213 | 225 | 239 | |
5 | 202 | 200 | 207 | 230 | |
2M | 6 | 208 | 233 | 231 | 225 |
7 | 187 | 298 | 194 | 218 | |
8 | 216 | 219 | 220 | 213 | |
9 | 205 | 234 | 227 | 230 | |
10 | 190 | 182 | 190 | 210 | |
1F | 11 | 173 | 170 | 187 | 181 |
12 | 151 | 146 | 152 | 158 | |
13 | 164 | 159 | 183 | 188 | |
14 | 176 | 176 | 181 | 200 | |
15 | 137 | 139 | 148 | 157 | |
2F | 16 | 352 | 169 | 167 | 180 |
17 | 165 | 155 | 144 | 159 | |
18 | 136 | 143 | 142 | 148 | |
19 | 151 | 142 | 139 | 153 | |
20 | 162 | 170 | 157 | 176 |
Table 5: Individual skin irritation scores.
Group number | Animal number | Reaction | Day of study | |||||||||||||||||||||||||||
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | |||
1M | 1 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
2 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
3 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | found dead in cage 6.10.83 | ||||||
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||||
4 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
5 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
2M | 6 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
7 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
8 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
9 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
10 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
1F | 11 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
12 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
13 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
14 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
15 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
2F | 16 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
17 | erythema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
18 | erythema | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
19 | erythema | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
20 | erythema | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 0 | 0 | 0 | |
oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 6: Individual haematology data; occasion: week 3.
Group and gender | Animal number | Hb (g/dl) | RBC (mil./cmm) | PCV (%) | MCH (pg) | MCHC (g/dl) | MCV (cum) | PT | WBC (1000/cmm) (%) | |||||
Sec | Total | N | L | M | E | B | ||||||||
1M | 1 | 16.1 | 7.15 | 44 | 22.5 | 37 | 61 | 11.9 | 10.5 | 1.68(16) | 8.61(82) | .10(1) | .10(1) | .00(0) |
2 | 15.9 | 7.09 | 43 | 22.4 | 37 | 60 | 12.7 | 17.6 | .35(2) | 17.07(97) | .18(1) | .00(0) | .00(0) | |
3 | 16.4 | 7.11 | 45 | 23.1 | 36 | 64 | 12.9 | 13.9 | 1.67(12) | 12.09(87) | .14(1) | .00(0) | .00(0) | |
4 | 15.6 | 6.92 | 43 | 22.5 | 36 | 62 | 11.4 | 16.2 | 1.46(9) | 14.58(90) | .16(1) | .00(0) | .00(0) | |
5 | 16.6 | 7.77 | 43 | 21.4 | 38 | 56 | 11.7 | 10.7 | 1.60(15) | 8.88(83) | .21(2) | .00(0) | .00(0) | |
mean: | 16.1 | 7.21 | 44 | 22.4 | 37 | 61 | 12.1 | 13.78 | 1.35(10) | 12.25(89) | .16(1) | .02(0) | .00(0) | |
S.D.: | 0.4 | 0.33 | 1 | 0.6 | 1 | 3 | 0.6 | 3.19 | .57(-) | 3.65(-) | .04(-) | .04(-) | .00(-) | |
2M | 6 | 16.1 | 7.31 | 43 | 22 | 38 | 59 | 13.1 | 16 | 1.12(7) | 14.72(92) | .16(1) | .00(0) | .00(0) |
7 | 16.8 | 7.39 | 45 | 22.7 | 37 | 61 | 11.9 | 14.4 | 1.49(12) | 10.66(86) | .25(2) | .00(0) | .00(0) | |
8 | 16.6 | 7.26 | 44 | 22.9 | 38 | 61 | 12.7 | 13.9 | .97(7) | 12.79(92) | .14(1) | .00(0) | .00(0) | |
9 | 15.9 | 6.68 | 43 | 23.8 | 37 | 65 | 11.6 | 16.4 | 1.48(9) | 14.76(90) | .16(1) | .00(0) | .00(0) | |
10 | 16.1 | 7.3 | 43 | 22.1 | 37 | 60 | 11.6 | 13.5 | 3.91(29) | 9.31(69) | .27(2) | .00(0) | .00(0) | |
mean: | 16.3 | 7.19 | 44 | 22.7 | 37 | 61 | 12.2 | 14.44 | 1.79(12) | 12.45(86) | .20(1) | .00(0) | .00(0) | |
S.D.: | 0.4 | 0.29 | 1 | 0.7 | 1 | 2 | 0.7 | 1.7 | 1.20(-) | 2.43(-) | .06(-) | .00(-) | .00(-) | |
1F | 11 | 16.3 | 7.27 | 43 | 22.4 | 38 | 59 | 11.1 | 12 | 1.08(9) | 10.68(89) | .12(1) | .12(1) | .00(0) |
12 | 16.5 | 7.31 | 44 | 22.6 | 38 | 60 | 11.1 | 10.8 | 1.08(10) | 9.61(89) | .11(1) | .00(0) | .00(0) | |
13 | 16.2 | 7.66 | 45 | 21.1 | 36 | 58 | 10.8 | 11.4 | .68(6) | 10.60(93) | .11(1) | .00(0) | .00(0) | |
14 | 15.9 | 6.92 | 42 | 23 | 38 | 61 | 10.3 | 12.4 | .87(7) | 11.53(93) | .00(0) | .00(0) | .00(0) | |
15 | 17.2 | 7.92 | 46 | 21.7 | 38 | 58 | 10.9 | 10.2 | 1.43(14) | 8.57(84) | .10(1) | .10(1) | .00(0) | |
mean: | 16.4 | 7.42 | 44 | 22.2 | 38 | 59 | 10.8 | 11.36 | 1.03(9) | 10.20(90) | .09(1) | .04(0) | .00(0) | |
S.D.: | 0.5 | 0.38 | 2 | 0.8 | 1 | 1 | 0.3 | 0.89 | .28(-) | 1.14(-) | .05(-) | .06(-) | .00(-) | |
2F | 16 | 16.1 | 7.43 | 44 | 21.7 | 37 | 59 | 10.8 | 23.3 | 3.73(16) | 19.11(82) | .23(1) | .23(1) | .00(0) |
17 | 16.6 | 7.78 | 44 | 21.3 | 38 | 56 | 10.9 | 7.4 | .89(12) | 6.44(87) | .00(0) | .07(1) | .00(0) | |
18 | 16.1 | 7.18 | 42 | 22.4 | 38 | 59 | 11.1 | 8 | .88(11) | 7.12(89) | .00(0) | .00(0) | .00(0) | |
19 | 15.8 | 7.16 | 42 | 22.1 | 38 | 59 | 10.8 | 9.3 | 1.67(18) | 7.53(81) | .09(1) | .00(0) | .00(0) | |
20 | 15.8 | 6.91 | 43 | 22.9 | 37 | 62 | 11 | 7.3 | 1.46(20) | 5.84(80) | .00(0) | .00(0) | .00(0) | |
mean: | 16.1 | 7.29 | 43 | 22.1 | 38 | 59 | 10.9 | 11.06 | 1.73(16) | 9.21(83) | .06(1) | .06(1) | .00(0) | |
S.D.: | 0.3 | 0.33 | 1 | 0.6 | 1 | 2 | 0.1 | 6.89 | 1.17(-) | 5.57(-) | .10(-) | .10(-) | .00(-) |
Table 7: Individual clinical chemistry data; occasion: week 3.
Group and gender | Animal number | GOT (Iu/l) | Alk.P (Iu/l) | Sodium (mEq/l) | Potassium (mEq/l) | Chloride (mEq/l) | Calcium (mEq/l) | Glucose (mg//dl) | B.U.N. (mg/dl) | Creatine (mg/dl) | T.Bilirubin (mg/dl) | Protein | A/G ratio | I.Phos (mg/dl) | |
Total (g/dl) | Albumin (g/dl) | ||||||||||||||
1M | 1 | 86 | 310 | 151 | 3.6 | 94 | 10.1 | 100 | 14 | 1.0 | 0.1 | 5.9 | 3.3 | 1.3 | 8.5 |
2 | 75 | 380 | 146 | 3.6 | 97 | 9.6 | 113 | 13 | 0.9 | 0.1 | 5.6 | 3.1 | 1.2 | 5.1 | |
3 | 90 | 374 | 139 | 3.8 | 90 | 10.4 | 114 | 12 | 1.0 | 0.0 | 6.0 | 3.3 | 1.2 | 7.5 | |
4 | 57 | 376 | 146 | 3.3 | 95 | 10.0 | 88 | 13 | 1.0 | 0.1 | 5.4 | 3.3 | 1.6 | 7.3 | |
5 | 75 | 430 | 147 | 3.4 | 93 | 9.9 | 126 | 14 | 1.0 | 0.0 | 6.1 | 3.5 | 1.3 | 7.6 | |
mean: | 77 | 374 | 146 | 3.5 | 94 | 10.0 | 108 | 13 | 1.0 | 0.1 | 5.8 | 3.3 | 1.3 | 7.2 | |
S.D.: | 13 | 43 | 4 | 0.2 | 3 | 0.3 | 15 | 1 | 0.0 | 0.1 | 0.3 | 0.1 | 0.2 | 1.3 | |
2M | 6 | 65 | 367 | 146 | 3.4 | 94 | 11.0 | 108 | 13 | 1.4 | 0.1 | 5.9 | 3.2 | 1.2 | 7.7 |
7 | 71 | 390 | 147 | 3.8 | 93 | 10.5 | 112 | 21 | 1.1 | 0.0 | 6.2 | 3.5 | 1.3 | 7.4 | |
8 | 58 | 327 | 148 | 3.4 | 95 | 10.3 | 126 | 19 | 1.1 | 0.0 | 6.0 | 3.4 | 1.3 | 7.3 | |
9 | 80 | 401 | 149 | 3.6 | 101 | 11.0 | 127 | 16 | 1.1 | 0.0 | 6.2 | 3.6 | 1.4 | 7.1 | |
10 | 77 | 492 | 151 | 3.2 | 99 | 10.7 | 92 | 17 | 1.1 | 0.1 | 6.2 | 3.5 | 1.3 | 6.3 | |
mean: | 70 | 395 | 148 | 3.5 | 96 | 10.7 | 113 | 17 | 1.2 | 0.0 | 6.1 | 3.4 | 1.3 | 7.2 | |
S.D.: | 9 | 61 | 2 | 0.2 | 3 | 0.3 | 14 | 3 | 0.1 | 0.1 | 0.1 | 0.2 | 0.1 | 0.5 | |
1F | 11 | 39 | 270 | 147 | 2.9 | 97 | 10.9 | 95 | 18 | 1.0 | 0.1 | 6.8 | 3.9 | 1.3 | 5.9 |
12 | 72 | 462 | 146 | 3.8 | 95 | 10.4 | 116 | 16 | 1.0 | 0.1 | 6.0 | 3.9 | 1.9 | 6.4 | |
13 | 75 | 325 | 149 | 2.7 | 98 | 9.9 | 100 | 16 | 1.1 | 0.1 | 6.2 | 3.6 | 1.4 | 5.3 | |
14 | 121 | 170 | 145 | 3.5 | 91 | 10.2 | 109 | 18 | 1.0 | 0.0 | 6.4 | 3.7 | 1.4 | 7.5 | |
15 | 135 | 20 | 146 | 3.3 | 99 | 10.3 | 99 | 15 | 1.1 | 0.0 | 6.6 | 3.7 | 1.3 | 6.4 | |
mean: | 88 | 285 | 147 | 3.2 | 96 | 10.3 | 104 | 17 | 1.0 | 0.1 | 6.4 | 3.8 | 1.5 | 6.3 | |
S.D.: | 39 | 116 | 2 | 0.4 | 3 | 0.4 | 9 | 1 | 0.1 | 0.1 | 0.3 | 0.1 | 0.3 | 0.8 | |
2F | 16 | 75 | 248 | 142 | 3.4 | 98 | 10.4 | 110 | 15 | 1.1 | 0.0 | 6.3 | 3.6 | 1.3 | 6.2 |
17 | 95 | 299 | 146 | 3.4 | 95 | 10.1 | 114 | 18 | 1.2 | 0.0 | 6.3 | 3.6 | 1.3 | 6.1 | |
18 | 80 | 381 | 142 | 3.2 | 97 | 10.0 | 114 | 15 | 1.2 | 0.1 | 6.5 | 3.6 | 1.2 | 5.8 | |
19 | 82 | 227 | 145 | 3.5 | 94 | 9.5 | 99 | 22 | 1.2 | 0.0 | 6.3 | 3.5 | 1.2 | 5.9 | |
20 | 88 | 348 | 149 | 3.1 | 93 | 10.5 | 121 | 17 | 1.1 | 0.0 | 6.4 | 3.8 | 1.5 | 5.7 | |
mean: | 84 | 301 | 145 | 3.3 | 95 | 10.1 | 112 | 17 | 1.2 | 0.0 | 6.4 | 3.6 | 1.3 | 5.9 | |
S.D.: | 8 | 65 | 3 | 0.2 | 2 | 0.4 | 8 | 3 | 0.1 | 0.0 | 0.1 | 0.1 | 0.1 | 0.2 |
Table 8: Individual organ weights of test animals.
Group and gender | Animal number | Body weight | Brain | Liver | Heart | Gonads | Adrenals | Kidneys | ||||||
Left | Right | Total | Left | Right | Total | Left | Right | Total | ||||||
1M | 1 | 341 | - | 14.15 | - | 1.589 | 1.636 | 3.225 | 0.028 | 0.033 | 0.061 | 1.27 | 1.30 | 2.57 |
2 | 319 | - | 11.71 | - | 1.364 | 1.395 | 2.759 | 0.034 | 0.031 | 0.065 | 0.98 | 0.98 | 1.96 | |
4 | 353 | - | 13.89 | - | 1.658 | 1.681 | 3.339 | 0.041 | 0.033 | 0.074 | 1.31 | 1.26 | 2.58 | |
5 | 295 | - | 12.23 | - | 1.601 | 1.601 | 3.202 | 0.022 | 0.027 | 0.049 | 1.11 | 1.18 | 2.29 | |
mean: | 327 | - | 12.99 | - | 1.553 | 1.578 | 3.131 | 0.031 | 0.031 | 0.062 | 1.17 | 1.18 | 2.35 | |
S.D.: | 25.6 | - | 1.206 | - | 0.13 | 0.126 | 0.255 | 0.008 | 0.003 | 0.01 | 0.53 | 0.142 | 0.291 | |
2M | 6 | 336 | - | 13.76 | - | 1.469 | 1.453 | 2.922 | 0.036 | 0.028 | 0.064 | 1.29 | 1.24 | 2.52 |
7 | 293 | - | 10.19 | - | 1.741 | 1.764 | 3.505 | 0.032 | 0.027 | 0.059 | 1.08 | 1.10 | 2.18 | |
8 | 337 | - | 16.94 | - | 1.552 | 1.550 | 3.102 | 0.029 | 0.037 | 0.066 | 1.30 | 1.37 | 2.67 | |
9 | 358 | - | 13.89 | - | 1.645 | 1.634 | 3.279 | 0.033 | 0.037 | 0.070 | 1.38 | 1.43 | 2.81 | |
10 | 303 | - | 11.54 | - | 1.633 | 1.611 | 3.244 | 0.036 | 0.041 | 0.077 | 1.07 | 1.03 | 2.10 | |
mean: | 325 | - | 13.26 | - | 1.608 | 1.602 | 3.210 | 0.033 | 0.034 | 0.067 | 1.22 | 1.23 | 2.46 | |
S.D.: | 26.7 | - | 2.577 | - | 0.103 | 0.114 | 0.217 | 0.003 | 0.006 | 0.007 | 0.14 | 0.171 | 0.308 | |
1F | 11 | 216 | - | 9.14 | - | 0.034 | 0.034 | 0.068 | 0.033 | 0.033 | 0.066 | 0.76 | 0.80 | 1.56 |
12 | 191 | - | 7.57 | - | 0.030 | 0.029 | 0.059 | 0.025 | 0.027 | 0.052 | 0.67 | 0.70 | 1.36 | |
13 | 206 | - | 7.62 | - | 0.040 | 0.039 | 0.079 | 0.037 | 0.034 | 0.071 | 0.70 | 0.73 | 1.43 | |
14 | 224 | - | 10.07 | - | 0.030 | 0.028 | 0.058 | 0.038 | 0.036 | 0.074 | 0.83 | 0.86 | 1.69 | |
15 | 186 | - | 7.14 | - | 0.028 | 0.028 | 0.056 | 0.036 | 0.034 | 0.070 | 0.66 | 0.73 | 1.39 | |
mean: | 205 | - | 8.31 | - | 0.032 | 0.032 | 0.064 | 0.034 | 0.033 | 0.067 | 0.72 | 0.76 | 1.49 | |
S.D.: | 16.1 | - | 1.243 | - | 0.005 | 0.005 | 0.010 | 0.005 | 0.003 | 0.009 | 0.072 | 0.066 | 0.137 | |
2F | 16 | 212 | - | 9.57 | - | 0.031 | 0.027 | 0.058 | 0.029 | 0.026 | 0.055 | 0.76 | 0.76 | 1.52 |
17 | 202 | - | 7.33 | - | 0.027 | 0.029 | 0.056 | 0.040 | 0.039 | 0.079 | 0.62 | 0.67 | 1.29 | |
18 | 188 | - | 6.64 | - | 0.024 | 0.018 | 0.042 | 0.031 | 0.022 | 0.053 | 0.66 | 0.71 | 1.37 | |
19 | 180 | - | 6.31 | - | 0.022 | 0.027 | 0.049 | 0.031 | 0.031 | 0.062 | 0.62 | 0.69 | 1.32 | |
20 | 214 | - | 8.32 | - | 0.027 | 0.031 | 0.058 | 0.032 | 0.034 | 0.066 | 0.71 | 0.75 | 1.46 | |
mean: | 199 | - | 7.63 | - | 0.026 | 0.026 | 0.053 | 0.033 | 0.030 | 0.063 | 0.67 | 0.72 | 1.39 | |
S.D.: | 14.9 | - | 1.329 | - | 0.003 | 0.005 | 0.007 | 0.004 | 0.007 | 0.010 | 0.060 | 0.037 | 0.097 |
Table 9: Group incidence: necropsy - all animals.
Tissue/observation | Group no.: | 1 | 2 | 1 | 2 |
Sex: | M | M | F | F | |
Abdominal cavity: gelatinous | 1 | 0 | 0 | 0 | |
Bladder: distension | 1 | 0 | 0 | 0 | |
Heart: pale area | 1 | 0 | 0 | 0 | |
Kidney: enlarged | 1 | 0 | 0 | 0 | |
Kidney: hydronephrosis | 1 | 1 | 0 | 1 | |
Prostate: red | 1 | 0 | 0 | 0 | |
Skin subcutis: sore | 1 | 5 | 4 | 2 | |
Skin subcutis: alopecia | 4 | 5 | 5 | 5 | |
Skin treated: sore | 0 | 0 | 0 | 1 | |
Tail: abnormal colour | 0 | 5 | 0 | 5 | |
Ureter: distension |
1 | 0 | 0 | 0 | |
Number of animals examined | 5 | 5 | 5 | 5 |
Table 10: Group incidence: histopathology - all animals.
Tissue/observation | Group no.: | 1 | 2 | 1 | 2 |
Sex: | M | M | F | F | |
Abdominal cavity: lesion | 1 | 0 | 0 | 0 | |
Adrenal hypertrophy | 1 | 0 | 0 | 0 | |
Bladder: cyctitis | 1 | 0 | 0 | 0 | |
Heart: myocarditis | 1 | 0 | 0 | 0 | |
Kidney: casts | 1 | 0 | 0 | 0 | |
Kidney: hydronephrosis | 1 | 1 | 0 | 1 | |
Kidney: Tubular regeneration | 1 | 2 | 0 | 0 | |
Kidney: mineralisation | 0 | 0 | 1 | 3 | |
Kidney: hyaline droplets | 3 | 3 | 0 | 0 | |
Liver: congestion | 1 | 0 | 0 | 0 | |
Liver: leucocyte foci | 4 | 4 | 2 | 5 | |
Prostate: prostatitis | 1 | 0 | 0 | 0 | |
Skin subcutis: acanthosis | 4 | 5 | 5 | 5 | |
Skin treated: not remarkable | 0 | 0 | 1 | 0 | |
Skin treated: erosion |
0 | 1 | 0 | 1 | |
Skin treated: acanthosis | 5 | 5 | 4 | 5 | |
Skin untreated: not remarkable | 0 | 0 | 4 | 3 | |
Skin untreated: acanthosis | 4 | 5 | 1 | 2 | |
Tail: abnormal colour | 0 | 5 | 0 | 5 | |
Ureter: distension | 1 | 0 | 0 | 0 | |
Number of animals examined |
5 | 5 | 5 | 5 |
Applicant's summary and conclusion
- Conclusions:
- NOAEL (dermal, rat, 28 days) ≥ 1000 mg/kg bw/day
- Executive summary:
The repeated dose toxicity of the test item was evaluated in a subacute, 28-day dermal study using a method comparable to the OECD Guideline 410 (1981). 5 male and 5 female Sprague-Dawley rats were exposed to 1000 mg/kg bw/day of test item to the shaved, dorsal region for 6 hours/day for 28 days, after which they were sacrificed. An additional 5 male and 5 female rats were administered the vehicle alone (4.0 ml/kg bw/day bi-distilled water) and monitored similarly in parallel to the test group. Mortality, skin irritation and clinical signs were monitored daily; body weight and food consumption were determined weekly. Blood samples were taken at 3 weeks and analysed for haematological and clinical chemistry parameters. Upon termination, necropsy, organ weight and histological examination were performed.
One control animal died spontaneously on day 22 due to a urinary tract obstruction. No change in clinical observations, body weight gains or food intakes related to treatment of the test item were observed. Skin irritation at the treatment site occurred in some animals exposed to 1000 mg/kg bw/day and in no controls: slight redness was observed in one female (days 2 to 4) and one male (days 23 to 28); slightly increased redness (grade 2) of the treatment site was observed in two females (days 22 to 29 in one and days 11 to 26 in the other); and very slight oedema was observed in one female (days 11 and 12). This did not indicate systemic toxicity. No significant changes in haematological and clinical chemistry parameters were observed. Brown skin discolouration to the tail was observed consistently. Histopathic examination of the treated skin site demonstrated erosions in 1 male and 1 female test animal. No consistent histopathological findings were observed which would suggest systemic toxicity due to test item application.
Based on the results observed, the NOEL for the substance in male and female rats is equal to or greated than 1000 mg/kg bw/day.
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