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Description of key information

In an OECD 422 study, toxicity was noted at 300 mg/kg, and was characterized by mortality (five animals in total) and various clinical signs.

Key value for chemical safety assessment

Toxic effect type:
concentration-driven

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 Jan 2012 - 10 Oct 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Also complies with OECD GLP regulations.
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
Qualifier:
according to
Guideline:
other: EPA, Health Effects Test Guidelines OPPTS 870.3650, Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, July 2000.
Deviations:
no
Qualifier:
according to
Guideline:
other: OECD Guidelines for Testing of Chemicals, Guideline 421, Reproduction/Developmental Toxicity Screening Test, July 1995.
Deviations:
no
Qualifier:
according to
Guideline:
other: The United States EPA Health Effects Test Guidelines, OPPTS 870.3550, Reproduction/Developmental Toxicity Screening Test, July 2000.
Deviations:
no
Principles of method if other than guideline:
In addition, the procedures described in the report essentially conform to the following guidelines:
- Commission regulation (EC) No 440/2008 Part B: Methods for the Determination of Toxicity and other Health Effects; B.7: "Repeated Dose (28 days) Toxicity (oral)". Official Journal of the European Union No. L142, May 2008.
- OECD Guidelines for Testing of Chemicals, Guideline 407, Repeated Dose 28-day Oral Toxicity Study in Rodents, October 2008.
- The United States EPA Health Effects Test Guidelines, OPPTS 870.3050, Repeated dose 28-day oral toxicity study in rodents, July 2000.
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): S-10793
- IUPAC nomenclature - Sodium diisobutyldithiophosphinate
- Lot S-20227-170B
- Appearance - White powder with lumps
- CAS No. 13360-78-6
- Molecular Formula - C8H18PS2.Na
- Molecular Weight - 232 g/mole
- Purity 93-94%
- Expiration date of the lot/batch: 16 December 2013
- Storage condition of test material: At room temperature in the dark
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Females nulliparous and non-pregnant: yes.
- Age at study initiation: Approximately 10 weeks.
- Weight at study initiation: mean weight at start of treatment was 282 gr (males) or 191 gr (females).
- Fasting period before study: no
- Housing:
Pre-mating: Animals were housed in groups of 5 animals/sex/cage in Macrolon cages.
Mating: Females were caged together with males on a one-to-one-basis in Macrolon cages.
Post-mating: Males were housed in their home cage with a maximum of 5 animals/cage. Females were individually housed in Macrolon cages.
General: Sterilised sawdust as bedding material and paper as cage enrichment were supplied.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 – 23.2°C
- Humidity (%): 34 - 65%
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Temporary fluctuations from the light/dark cycle (with a maximum of 1hour) occurred due to performance of pupillary reflex tests in the room. Based on laboratory historical data, these fluctuations were considered
not to have affected the study integrity.
Temporary deviations from the minimum level of daily mean relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: From: 21 February - 10 April 2012
Route of administration:
oral: gavage
Details on route of administration:
Plastic feeding tube
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1%
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
Formulations (w/w) were prepared daily within 6 hours prior to dosing and were homogenized to a visually acceptable level. No adjustment was made for the purity of the test substance.
Storage conditions of formulations: At ambient temperature.

VEHICLE
- Justification for use and choice of vehicle: Based on trial formulations performed at NOTOX.
- Dose volume: 5 mL/kg body weight. Actual dose volumes were calculated according to the latest body weight.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analyses were conducted once during the pilot study and were conducted twice during the treatment phase of the main study (Days 1 and 14; 21 February and 5 March 2012) using the HPLC-UV method. Samples of formulations were analyzed for homogeneity (highest and lowest concentration) and accuracy of preparation (all concentrations). Stability in vehicle over 6 hours at room temperature was also determined during the first analysis (highest and lowest concentration). The accuracy of preparation was considered acceptable if the mean measured concentrations were 90-110% of the target concentration for suspensions. Homogeneity was demonstrated if the coefficient of variation was ≤ 10%. Formulations were considered stable if the relative difference before and after storage was maximally 10%.

The concentrations analysed in the Day 1 and Day 14 formulations of Group 2, Group 3 and Group 4 were in agreement with target concentrations (i.e. mean accuracies between 90% and 110%) and no test substance was detected in the Group 1 formulations. The formulations from Days 1 and 14 of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%) and formulations at the entire range were stable when stored at room under normal laboratory light conditions for at least 6 hours (stability was only conducted for Day 1 formulations).

Additional details are given in the attached document that indicates pages 172-174 from the study report.
Duration of treatment / exposure:
Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 43-49 days, i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation. One females of Group 1 and one of Group 3 were not dosed during littering.
Frequency of treatment:
Once daily, 7 d/w
Dose / conc.:
30 mg/kg bw/day (actual dose received)
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
300 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Dose levels were based on results of the dose range finding study (NOTOX Project 498685) where 500, 1000, 125 and 250 mg/kg were tested. Since the relevant effects at 125 and 250 mg/kg completely resolved after a few days of treatment, the dose levels for the main study were: 30, 100 and 300 mg/kg body weight.
The peak period of clinical signs occurred between immediately after dosing up to 1 hour after dosing. As such, clinical observations will be conducted between 0-1 hours after dosing in the main study.)

- Fasting period before blood sampling for clinical biochemistry: overnight with a maximum of 20 hours
Positive control:
No.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS:
- Time schedule: At least twice daily. Animals showing pain, distress or discomfort, which was considered not transient in nature or was likely to become more severe, were sacrificed for humane reasons based on OECD guidance document on humane endpoints (ENV/JM/MONO/ 2000/7). The circumstance of any death was recorded in detail.

DETAILED CLINICAL OBSERVATIONS:
- Time schedule: Daily, detailed clinical observations were conducted for all animals, and were started between immediately after up to 1 hour (e.g. 0-1 hour) after dosing (on the peak period of anticipated effects after dosing). Once prior to start of treatment and at weekly intervals during the treatment period (between immediately after up to 1 hour (e.g. 0-1 hour) after dosing) this was also performed outside the home cage in a standard arena. Arena observations were not performed when the animals were mating, or housed individually. The time of onset, grade and duration of any observed sign was recorded. Signs were graded for severity

BODY WEIGHT:
- Time schedule for examinations: Males and females were weighed on the first day of exposure and weekly thereafter. Mated females were weighed on Days 0, 4, 7, 11, 14, 17 and 20 post-coitum, and during lactation on Days 1 and 4. In order to monitor the health status Group 4 males were weighed more often. This was documented in the study raw data.

FOOD CONSUMPTION:
- Weekly, for males and females. Food consumption was not recorded during the mating period. Food consumption of mated females was measured on Days 0, 4, 7, 11, 14, 17 and 20 post-coitum and on Days 1 and 4 of lactation.

FOOD EFFICIENCY:
- (average food consumption [per animal per day]/average body weight per cage)x1000

WATER CONSUMPTION : No.
Subjective appraisal was maintained during the study, but no quantitative investigation introduced as no effect was suspected.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY:
- Time schedule for collection of blood: immediately prior to scheduled post mortem examination.
- Anaesthetic used for blood collection: Yes (iso-flurane)
- Animals fasted: Yes (with a maximum of 20 hours). Water was provided.
- How many animals: 5 animals/sex/group
- Parameters checked were: According to test guidelines

CLINICAL CHEMISTRY:
- Time schedule for collection of blood: immediately prior to scheduled post mortem examination.
- Animals fasted: Yes (with a maximum of 20 hours). Water was provided.
- How many animals: 5 animals/sex/group
- Parameters checked were: According to test guidelines

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION:
- Time schedule for examinations: The selected males were tested during Week 4 of treatment and the selected females were tested during lactation (all before blood sampling).
- Dose groups that were examined: all
- Battery of functions tested: According to test guidelines

* 5 animals/sex/group were randomly selected at allocation for functional observations, clinical pathology, macroscopic examination (full list), organ weights (full list) and histopathology (see also respective paragraphs). Only females with live offspring were selected.
Sacrifice and pathology:
GROSS PATHOLOGY:
- All males and the selected 5 females/group were fasted overnight (with a maximum of 20 hours) prior to planned necropsy, but water was provided. Animals surviving to scheduled necropsy and all moribund animals were deeply anaesthetised and subsequently exsanguinated.
- Selected 5 animals/sex/group and all animals that died spontaneously or were killed in extremis: According to test guidelines
- All remaining females which failed to deliver and the remaining males: According to test guidelines
- All animals were subjected to macroscopic examination of the cranial, thoracic and abdominal tissues and organs, with special attention being paid to the reproductive organs. Descriptions of all macroscopic abnormalities were recorded.
- Samples of the tissues and organs were collected and fixed in 10% buffered formalin

Several animals were necropsied later than after a maximum of 20 hours fasting, i.e. with a maximum of approximately 21 hours. The fasting period was only slightly longer and was considered not to have adversely affected the macroscopic or microscopic findings.

ORGAN WEIGHTS
- Selected 5 animals/sex/group: According to test guidelines
- All remaining males: Epididymides and Testes

HISTOPATHOLOGY:
- According to test guidelines

The partial list of organs was taken from one male of Group 4, where the full list should have been taken. A few other organs were not available from individual animals for histopathology. Missing tissues are listed in raw data and pathology report. There is sufficient data for a thorough evaluation.
Statistics:
The following statistical methods were used to analyse the data:
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (Dunnett, 1955) (many-to-one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex. (Ref. 1)
- The Steel-test (Miller, 1981) (many-to-one rank test) was applied if the data could not be assumed to follow a normal distribution. (Ref. 3)
- The Fisher Exact-test (Fisher, 1950) was applied to frequency data. (Ref. 2)
- The following additional methods of statistical analysis were used: Motor activity data was subjected to the Kruskal-Wallis nonparametric ANOVA test (Ref. 4) to determine intergroup differences followed by the Wilcoxon test (Ref. 5) to compare the treated groups to the control group.

All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance. Group means were calculated for continuous data and medians were calculated for discrete data (scores) in the summary tables. No statistical analysis was performed on histopathology findings.

References:
Ref. 1 Dunnett C.W., A Multiple Comparison Procedure for Comparing Several Treatments with a Control, J. Amer. Stat. Assoc. 50, 1096-1121 (1955).
Ref. 2 Fisher R.A., Statistical Methods for Research Workers, Oliver and Boyd, Edinburgh (1950).
Ref. 3 Miller R.G., Simultaneous Statistical Inference, Springer Verlag, New York (1981).
Ref. 4 Kruskal W.H. and Wallis W.A.. Use of ranks in one-criterion variance analysis. Journal of the American Statistical Association 47 (260): 583-621, December (1952).
Ref. 5 Wilcoxon, F. Individual comparisons by ranking methods. Biometrics, 1, 80-83 (1945).
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
At 300 mg/kg hunched posture and salivation were noted for all animals. Piloerection, swelling of the abdominal area and flat gait were also noted for a few animals of both sexes, though at a much lower frequency than hunched posture and salivation. Lastly, lethargy, pale appearance and diarrhoea were noted for individual animals at this dose level. Salivation was also seen for all animals at 100 mg/kg, and for one female and four males at 30 mg/kg. In all cases, including the animals at 300 mg/kg, this was likely a physiological response due to the taste of the test substance instead of a sign of systemic toxicity. Piloerection and hunched posture were noted on two occasions for one animal at 30 mg/kg. No toxicological relevance was attributed to these findings as they occurred only on two occasions for a single animal at this dose level. Incidental findings that were noted for control and/or treated animals included rales, scabs and alopecia. These findings occurred within the range of background findings encountered for rats of this age and strain which are housed and treated under the conditions in this study. At the incidence observed, they were not considered to be toxicologically relevant..
Mortality:
mortality observed, treatment-related
Description (incidence):
Two males and one female died spontaneously and two additional females were killed in extremis at 300 mg/kg. The males died after 12 and 13 days of treatment, respectively, and the female died after 29 days on test. The females killed in extremis were euthanized after 30 and 41 days on test, respectively. These animals had only slight weight loss in the time before their deaths. Clinical signs including hunched posture, salivation, piloerection, flat gait, abdominal swelling and pale appearance were noted for some or all animals before their deaths. One female at 100 mg/kg was euthanized because she had a total litter loss (her litter consisted of a single pup). One female that was euthanized in extremis also had a total litter loss where her litter of three pups was found dead at the first litter check.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weights and body weight gains were significantly lower beginning on Day 8 of the premating period until the end of the treatment period for males at 300 mg/kg. While the differences from controls were not statistically significant, females at this dose level also had lower body weights and gains for most of the post coitum and lactation periods (body weight gains were significantly lower for females on Days 4 and 11 during the post coitum period only). One female of Group 1, one female of Group 3 and one of Group 4 had lower body weight gains throughout the post-coitum period, which was attributable to their pregnancy status. These females were all pregnant but did not produce litters with live pups. The female of Group 1 had implantation sites only, the female of Group 3 was found with a single fetus in the uterus (she never delivered), and the female of Group 4 gave birth to three pups that were all dead at the first litter check. No other toxicologically relevant changes in body weights and body weight gain were noted up to 100 mg/kg. Absolute body weights were lower for males at 30 mg/kg during Day 8 of the premating period up to Day 1 of the mating period. This was not considered to be toxicologically relevant because the difference from controls was only slight and occurred in the absence of a dose response effect.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
At 300 mg/kg absolute and relative food consumption was significantly lower than controls on Days 7-11 of the post coitum period. Slightly lower absolute and relative values than control values were noted over Days 1-8 of the premating period for both sexes (Days 1-15 for males, absolute food consumption only), and for females on Days 0-4 and 1-4 of the post coitum and lactation periods, respectively. These effects were seen at the beginning of the treatment period and were mostly resolved over time, though they were treatment related. There were no other effects on absolute or relative food consumption noted.
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Haematology parameters were affected for females at 300 mg/kg only. Compared to controls, significantly lower values were obtained for eosinophils, haemoglobin, red blood cells and mean corpuscular haemoglobin concentration (MCHC) and significantly higher mean corpuscular volume (MCV) values were seen. When taken together with slightly increased (not statistically significant) reticulocytes and red blood cell distribution width (RDW), these findings are suggestive of slight anemia. There were no other toxicologically relevant effects on haematology parameters up to 100 mg/kg.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
At 300 mg/kg, a significant decrease in alkaline phosphatase (ALP) and total protein were noted for males, along with significantly lower creatinine and inorganic phosphate levels for females only. Females at 300 mg/kg also had significantly higher alanine aminotransferase (ALAT; also for females at 100 mg/kg) and aspartate aminotransferase (ASAT) compared to controls. These effects were treatment related but in the absence of any effects on the liver or kidneys, the toxicological relevance of these changes are doubted. The higher ALAT and bile acid means for males at 300 mg/kg were both attributable to very high values obtained for one male of Group 4 and thus these differences were not considered to be toxicologically relevant. No other toxicologically relevant changes in clinical biochemistry parameters were seen.
Urinalysis findings:
not examined
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
Both total movements and ambulatory counts were reduced for males and females at 300 mg/kg compared to control animals (only significant for male total movements). While lethargy and flat gait were only noted for a few animals in this group, a relationship to treatment could not be excluded. All groups had a habituation profile with very high activity in the first interval that decreased over the duration of the test period. Hearing ability, pupillary reflex, static righting reflex and grip strength were normal for all animals.
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There were no toxicologically relevant changes in organ weights or organ to body weight ratios seen with treatment up to 300 mg/kg. Males at 300 mg/kg had significantly lower terminal body weights with higher brain- and testes to body weight ratios. These were secondary to their comparatively lower body weights, and were not considered toxicologically relevant. Females at 100 mg/kg had significantly higher absolute kidney weights. These were attributable to their slightly higher body weights and was not related to treatment.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
At 300 mg/kg, there were several treatment related findings noted at the macroscopic examination. Findings noted for animals that died or were euthanized before the scheduled necropsy included emaciation, advanced autolysis, enlarged caecum, indurated contents of the caecum, red discoloration of the thymus, reduced size of the thymus, dark red discoloration of the mandibular lymph node, dilation of the GI tract or common bile duct, irregular surface of the forestomach and watery-cloudy contents of the small intestine. Macroscopic findings noted for surviving animals at 300 mg/kg included emaciation, enlarged caecum, reduced size of the thymus, reddish, dark red or black discoloration of and enlargement of the mandibular lymph node and/or pancreatic lymph node, enlarged adrenal glands, dilation of the ileum, and reduced size of the prostate and/or seminal vesicles. At 100 mg/kg, a thickened uterus and bluish contents in the right uterine horn were noted for one female of Group 3 who had a total litter loss. One other female of Group 3 was found with one fetus in the right uterine horn. This female began delivery, though no pups were found the next day. Subsequent examination revealed only one implantation site for this female. These findings were not considered to be attributable to treatment with S-10793. Incidental findings included reduced size of the right testis and epididymis, yellowish, soft nodule on the tail of the left epididymis, pelvic dilation of the kidney, and alopecia of the flank, inguinal, foreleg or abdominal regions.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
There were treatment-related microscopic findings in the 300 mg/kg treated rats in the following organs/tissues:
Thymus: Lymphoid atrophy was noted in 5/5 unscheduled deaths (one minimal, four moderate) and in the surviving rats at an increased incidence (5/9) and/or severity (up to moderate).
Stomach:
- Hyperplasia of the forestomach was noted in 5/5 unscheduled deaths (three slight, two moderate) and in the surviving rats at an increased incidence (5/9) and/or severity (up to slight).
- Ulceration of the forestomach was noted in 2/5 unscheduled deaths (up to slight).
- Hyperplasia of the limiting ridge was noted in 1/5 unscheduled deaths (slight) and in the surviving rats at an increased incidence (6/9) and/or severity (up to slight).
- Inflammation of the forestomach was noted in 1/5 unscheduled deaths (slight).
- Edema of the forestomach was noted in 1/5 unscheduled deaths (slight).
- Hyperkeratosis of the forestomach was noted in 1/10 of the surviving rats (minimal).
Skeletal muscle:
- Myofiber degeneration/regeneration was noted in 3/5 unscheduled deaths (one minimal, two slight, females only) and in the surviving females at an increased incidence (5/5) and/or severity (up to moderate).
Mesenterial lymph node:
- Congestion/erythrophagocytosis was noted in 5/5 unscheduled deaths (two slight, three moderate) and in the surviving female rats at an increased incidence (5/9) and/or severity (up to moderate).
The recorded microscopic findings in the 0 mg/kg, 30 mg/kg and 100 mg/kg treated animals were within the normal range of background alterations encountered in Wistar (Han) rats of this age and strain and therefore not regarded as test item related. There were no morphological findings in the reproductive organs of either sex in the 0 mg/kg (Group 1), 30 mg/kg (Group 2), 100 mg/kg (Group 3) and 300 mg/kg (Group 4) treated rats which account for their infertility, failure to deliver healthy pups or reduction in litter size. Furthermore, the spermatogenic staging profiles were normal for all males evaluated.
Histopathological findings: neoplastic:
not examined
Dose descriptor:
NOAEL
Remarks:
Parental generation
Effect level:
100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Critical effects observed:
no
Conclusions:
Treatment with the test material by oral gavage in male and female Wistar Han rats at dose levels of 30, 100 and 300 mg/kg body weight/day revealed parental toxicity at 300 mg/kg body weight/day. Based on these results, the No Observed Adverse Effect Level (NOAEL) was 100 mg/kg/day.
Executive summary:

A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of the test material was conducted in rats by oral gavage following OECD TG 422 and under GLP conditions.

The test material was administered by daily oral gavage to male and female Wistar Han rats at dose levels of 30, 100 and 300 mg/kg/day (10 animals/sex/dose; dose levels based on a dose range finding study). Males were exposed for 2 weeks prior to mating, during mating, and up to termination (for 29 days). The females were exposed for 2 weeks prior to mating, during mating, during post-coitum, and at least 4 days of lactation (for 43-49 days). Formulation analysis showed that the formulations were prepared accurately, were homogenous and were stable for at least 6 hours at room temperature.

Toxicity was noted at 300 mg/kg, and was characterized by mortality (five animals in total), clinical signs, reduced body weights, changes in haematology parameters indicative of slight anemia, macroscopic findings and microscopic findings of the thymus, stomach, skeletal muscle and mesenteric lymph node. The irritating nature of the test substance may have contributed to some of these findings.

No toxicologically significant changes were noted in any of the remaining parental parameters investigated in this study (i.e. food consumption, clinical biochemistry and organ weights).

In conclusion, treatment with the test material by oral gavage in male and female Wistar Han rats at dose levels of 30, 100 and 300 mg/kg body weight/day revealed parental toxicity at 300 mg/kg body weight/day. Based on these results, the No Observed Adverse Effect Level (NOAEL) was 100 mg/kg/day.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Toxicity was noted at 300 mg/kg, and was characterized by mortality (five animals in total), clinical signs, reduced body weights, changes in haematology parameters indicative of slight anemia, macroscopic findings and microscopic findings of the thymus, stomach, skeletal muscle and mesenteric lymph node. The irritating nature of the test substance may have contributed to some of these findings. No toxicologically significant changes were noted in any of the remaining parental parameters. The No Observed Adverse Effect Level (NOAEL) was determined to be 100 mg/kg.

Justification for classification or non-classification

Not Classified. - Based on available data and/or professional judgment, the classification criteria are not met.