Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute toxicity:
Oral LD50 612 mg/kg- bw in female rats (OECD TG 401)
Dermal LD50 251 mg/kg-bw in male and female rats (OECD TG 402)
Inhalation LC50 157 ppm in female rats (OECD TG 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, New York
- Age at study initiation: 55 days (males); 65 days (females)
- Weight at study initiation: 184-232 g (males); 187-217 g (females)
- Fasting period before study: overnight
- Housing: 1/cage in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rodent chow 5002 (C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 74-74 degrees F (23-24 degrees C)
- Humidity (%): 41-46%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark


IN-LIFE DATES: From: July 21, 1992 To: August 6, 1992
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: corn oil dispersion
- Amount of vehicle (if gavage): corn oil dispersion 10 mL/kg
- Justification for choice of vehicle: corn oil is a standard vehicle
- Lot/batch no. (if required): 80H0835
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION (if unusual): dispersed in corn oil using a magnetic stirring bar


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A
Doses:
50, 250, 500, 750, 1000, 1500 mg/kg
No. of animals per sex per dose:
60
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: 0.5, 1, 2, and 4 hr after dosing and once daily for 14 days; Body weights were recorded Day 0 prior to dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 95% confidence limits were calculated from the logarithm of the doses and the incidence of maortality using the Thompson moving average procedure (W.R. Thompson, "Use of Moving Averages and Interpolation to Estimate Median-Effective Dose", Bacteriol. Rev. 11, pp. 115-145, 1947). Slope estimates were obtained using the methods outlined by Weil (C.S. Weil, "Economical LD50 and Slope Determinations", Drug and Chemical Toxicology 6(6), pp. 595-603, 1983). All calculations were performed using the Statistical Analysis System on an IBM mainframe computer (SAS Institute Inc. SAS User's Guide: Basics, Version 5 Edition, Cary, NC:SAS Institute Inc., 1985)
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
612 mg/kg bw
95% CL:
442 - 848
Sex:
male
Dose descriptor:
LD50
Effect level:
1 177 mg/kg bw
95% CL:
974 - 1 422
Mortality:
- Time of death: Males - 2 at 1000 mg/kg on day 1; 1 at 1500 mg/kg 1 hr post-dosing (day 0); 3 at 1500 mg/kg on day 1; 1 at 1500 mg/kg on day 2. Females - 2 at 500 mg/kg 2 hr post-dosing (day 0); 1 at 500 mg/kg 4 hr post-dosing (day 0); 1 at 500 mg/kg on day 1; 1 at 750 mg/kg 1 hr post-dosing (day 0); 1 at 750 mg/kg 2 hr post-dosing (day 0); 5 at 1500 mg/kg 1 hr post-dosing (day 0); 1 at 1500 mg/kg 2 hr post-dosing (day 0).
- Number of deaths at each dose: (number of deaths/number treated)
Dose (mg/kg) 50 250 500 750 1000 1500
Males --- 0/6 0/6 0/6 2/6 5/6
Females 0/6 0/6 4/6 2/6 --- 6/6
Clinical signs:
No clinical signs related to test substance were observed in the 250-mg/kg group for males and in the 50- and 250-mg/kg groups for the females. Clinical signs indicative of neurotoxicity (abnormal gait, tremors, and convulsions) were observed at dose levels of 500 mg/kg and greater in survivors as well as decedents. Surviving animals recovered from the neurotoxic effects by day 2 of the study. Other clinical signs related to the test substance observed in survivors as well as decedents included prostration, abnormal breathing patterns, scant or no feces and ptosis.
Body weight:
There were no apparent dose-related body weight effects in this study.
Gross pathology:
Necropsy of the decedents revealed numerous gastro-intestinal effects related to the test substance. Necropsy of the survivors revealed no gross changes related to the test substance.
Other findings:
- Potential target organs: gastro-intestinal tract
- Other observations: Statistically significant sex-related difference in mortality observed.

Since there was a statistically significant sex-related difference in mortality observed, the LD50 was calculated separately for males and females.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral LD50 in female rats is 612 mg/kg.
Executive summary:

The acute oral toxicity of the test material was assessed in Crl:CD BR rats. The test material was dispersed in corn oil and gavaged to five groups of male rats (6/group) at 250, 500, 750, 1000 or 1500 mg/kg and five groups of female rats (6/group) at 50, 250, 500, 750 and 1500 mg/kg. The corn oil dispersions were dosed at a constant volume of 10 ml/kg body weight. Mortality was observed in the 1000 and 1500 mg/kg dose groups in males and in the 500, 750 and 1500 mg/kg dose groups in females. No clinical signs related to test substance were observed in the 250 mg/kg group for males and in the 50 and 250 mg/kg groups in females. Clinical signs at dose levels of 500 mg/kg and greater in survivors as well as decedents. Surviving animals recovered from the neurotoxic effects by day 2 of the study. Other clincial signs related to the test substance observed in survivors as well as decedents included prostration, abnormal breathing patterns, scant or no feces and ptosis. There were no apparent dose-related body weight effects in this study. Necropsy of the decedents revealed numerous gastro-intestinal effects related to the test substanced. Necropsy of the survivors revealed no gross changes related to the test substance. the no observed effect level (NOEL) was 250 mg/kg.

Since there was a statistically significant sex-related difference in mortality observed, the LD50 in males rats was 1177 mg/kg with 95% confidence limits of 974 and 1422 mg/kg. The acute oral LD50 in female rats was 612 mg/kg with 95% confidence limits oof 442 and 848 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
612 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
For two days the temperature was below the range stated in the protocol
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Chrales River-Kingston, Stone Ridge, New York
- Age at study initiation: 8 weeks (males); 10 weeks (females)
- Weight at study initiation: 234-274 g (males); 219-267 g (females)
- Fasting period before study: no data
- Housing: 1/cage in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI certified rodent chow 5002 (C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 degrees C
- Humidity (%): 38-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark


IN-LIFE DATES: From: October 31, 2000 To: November 21, 2000
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 240-L Plexiglas and stainless steel chamber
- Exposure chamber volume: 240-L
- Method of holding animals in test chamber: nose-only restraining tubes (15 cm length x 5 cm diameter PVC pipe). Each animal was restrained in the tube with a neoprene stopper in the rear and a plastic funnel in the front.
- Source and rate of air: conditioned laboratory air airflow rate approximately 100 to 118 L/min
- Method of conditioning air: not aplicable
- System of generating aerosols: An FMI G20 RHOCKC Micropump (Fluid Metering, Oyster Bay, NY) delivered the neat test material to the top of a glass 20 inch counter current vapor generator. The test material dripped onto a heat coil (set at 120 degrees F, 140 degrees F or 130 degrees F for the 91, 231 and 151 ppm exposures, respectively) contained inside the glass counter current vapor generator. As the test material vaporized, compressed air (11 psi) forced the vaporized test material up through a glass manifold (wrapped in heat tape which maintained a temperature of 43 to 61 degrees C). The glass manifold delivered the vaporized test material into the top of the exposure chamber. Vaproized test material was directed into the top of a 240-L Plexiglas and stainless steel chamber and mixed with the conditioned laboratory air drawn through a HEPA particle filter located on the chamber inlet. The exposure atmosphere was exhausted at the bottom of the exposure chamber and passed through a series of filters (coarse particulate, HEPA, charcoal filters and an aqueous scrubber) before being released at roof level of the building. Chamber airflow was monitored continuously by measuring the pressure drop across a critical orifice plate located in the chamber exhaust duct.
- Method of particle size determination: no data
- Treatment of exhaust air: exhausted at the bottom of the exposure chamber and passed through a series of filters (coarse particulate, HEPA, charcoal filters and an aqueous scrubber) before being released at roof level of the building.
- Temperature, humidity, pressure in air chamber: 24.6 to 25.7 degrees C, 33% humidity


TEST ATMOSPHERE
- Brief description of analytical method used: The test material vapor in the inhalation chamber was directly sampled using silicosteel tubing connected to a 6 port gas sampling valve on a Gas Chromatograph (GC). Two samples/hour were taken during each exposure period to insure adequate characterization of the atmosphere. The saturated vapor concentration of the test material was determined using the same sampling and analytical methodology used to measure the test material concentrations during the animal exposures. The saturated vapor concentration was measured at room temperature (19°C) and at a temperature similar to that measured in the test atmosphere during the inhalation exposures (24°C). The saturated vapor concentration of the test material at room
temperature was obtained by placing 20 ml of the test material into a Tedlar bag and equilibrating the bag overnight at room temperature. The saturated vapor concentration of the test material at 24°C was obtained by placing 20 ml of the test material into a Tedlar bag and placing the bag in an oven overnight. The Tedlar bags were directly sampled using silicosteel tubing connected to a 6 port gas sampling valve on a Gas Chromatograph (GC).
- Samples taken from breathing zone: yes


VEHICLE not applicable; no vehicle

TEST ATMOSPHERE (if not tabulated) Not applicable- vapor study
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):


CLASS METHOD (if applicable) not applicable
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC
Duration of exposure:
4 h
Concentrations:
91, 151, 231 ppm
No. of animals per sex per dose:
30
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for signs of intoxication during the exposure period and daily for 14 days following exposure. Body weights were recorded on days 0, 7, and 14 during the fourteen-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The female LC50, 95% confidence limits and slope were calculated from the logarithm of the doses and the incidences of mortality using a SAS PROBIT procedure (SAS Institute Inc. SAS User's Guide: Statistics, Version 6 Edition, p 1324 - 1350. Cary, NC: SAS Institute Inc., 1990) based on the method of D.J. Finney (Probit Analysis, Thrid Edition, London: Cambridge Universtiy Press, 1971)
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 157 ppm
95% CL:
> 90 - < 249
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
157 ppm
95% CL:
> 90 - < 249
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
> 231 ppm
Exp. duration:
4 h
Mortality:
- Time of death: Males - 2 at 231 ppm during exposure period (day 0). Females - 1 at 151 ppm during exposure period (day 0); 1 at 151 ppm on day 1; 3 at 231 ppm during exposure period (day 0); 1 at 231 ppm on day 1.
- Number of deaths at each dose: (number of deaths/number treated)
Dose (ppm) 91 151 231
Males 0/5 0/5 2/5
Females 0/5 2/5 4/5
Clinical signs:
other: Numerous clinical signs of toxicity were noted in all exposure levels in both sexes beginning upon removal from the chamber and continuing through day 7. These clinical signs included: respiratory noise, labored breathing, gasping, abnormal gait, ataxia,
Body weight:
There was no effect on body weight in either sex at any exposure level when compared to historical control values.
Gross pathology:
Necropsy of the decedents revealed dark, mottled and/or reddened lungs, distended stomachs, and thymus reddened and/or having multiple red foci. Necropsy of the survivors revealed no gross changes.
Other findings:
- Potential target organs: lungs
- Other observations: SEX-SPECIFIC DIFFERENCES: Even though the results did not indicate a statistically significant sex-related difference in mortality across dose groups for males and females, the LC50 was calculated on the female mortality incidences at each dose since at least 50% mortality was not observed in males at the highest exposure level (231 ppm).
Interpretation of results:
Category 2 based on GHS criteria
Executive summary:

The acute inhalation toxicity of the test material was assessed in Crl:CD®BR rats. Three groups of five male and five female rats received a single 4-hr noseonly inhalation exposure to the test material vapor concentrations of 91, 151 and 231 ppm equivalent to 0.69, 1.14, and 1.75 mg test material/L of air. The saturated vapor concentration of the test material was determined using the same sampling and analytical methodology used to measure vapor concentration during the inhalation exposures. Measurements were made at approximately room temperature and at a temperature similar to that of the test atmosphere during the animal exposures. Exposure-related mortality occurred in animals exposed to the test material at 151 ppm and above. No deaths occurred in the 91 ppm group or in males at 151 ppm. The total mortality incidences (no. deaths/no. treated) for males and females in this study were:

Dose (ppm) 91 151 231

Males 0/5 0/5 2/5

Females 0/5 2/5 4/5

The LC50 value was calculated from the female mortality incidence data. Numerous clinical signs of toxicity were noted in all exposure levels in both sexes beginning upon removal from the chamber and continuing through day 7. These clinical signs included: respiratory noise, labored breathing, gasping, abnormal gait, ataxia, tremors, passiveness, scant feces, arched back, prostration and/or yellow/brown stained anogenital area. There was no effect on body weight among survivors in either sex at any exposure level. Necropsy of the decedents revealed dark, mottled and/or reddened lungs, distended stomachs, and thymus reddened and/or having multiple red foci. Necropsy of the survivors revealed no gross changes. The acute inhalation LC50 for the test material in female rats was 157 ppm (1.19 mg/L) with 95% confidence limits of 90 to 249 ppm. The acute inhalation LC50 for the test material in male rats was greater than 231 ppm (1.75 mg/L). The saturated vapor concentration of the test material was 150 ppm at 19°C (room temperature) and 220 ppm at 24°C (similar to temperature of test atmospheres).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 190 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River-Kingston, Stone Ridge, New York
- Age at study initiation: approximately 55 days old (males); approximately 65 days old (females)
- Weight at study initiation: 223 to 248 g (males); 206 to 243 g (females)
- Fasting period before study: not reported
- Housing: one/cage in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rodent chow 5002(C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 24 degrees C
- Humidity (%): 41 to 46%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark


IN-LIFE DATES: From: July 21, 1992 To: August 4, 1992
Type of coverage:
occlusive
Vehicle:
other: Neutral Oil 100 N
Details on dermal exposure:
TEST SITE
- Area of exposure: entire trunk between the flank and shoulders- approximatelly 6 x 6 cm
- % coverage: not reported
- Type of wrap if used: polyethylene sheet covered with Elastoplast (Beiersdorf, Inc. Norwalk, Connecticut) and PEG (Becton-Dickinson Co. Franklin Lakes, New Jersey) elastic bandages secured in place with adhesive tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 24 hours, the backs were wiped with water-soaked paper towels.
- Time after start of exposure: after 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 mL/kg
- Concentration (if solution): none
- Constant volume or concentration used: yes
- For solids, paste formed: not appicable


VEHICLE Neutral Oil 100 N- contains 100% of refined paraffinic distillate
- Amount(s) applied (volume or weight with unit): 2.0 mL/kg
- Concentration (if solution): none
- Lot/batch no. (if required): 8-0419
- Purity: no data
Duration of exposure:
24 hour
Doses:
50, 200, and 400 mg/kg
No. of animals per sex per dose:
36
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs observed 0.5, 1, 2, and 4 hr after dosing and once daily for 14 days. Body weights recorded on day 0 (prior to dosing) and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The mortality incidences of males and females were compared across doses with a categorical data modelling procedure using SAS CATMOD (SAS Institute, Inc. SAS User's Guide: Statistics, Version 5 Edition, p 171-253. Cary, NC: SAS Institute Inc., 1985). The criterion of statistical significance was 0.05. If the results indicate a significant difference between the mortality responses for males and females, the LD50 is calculated separately by sex; otherwise the LD50 is calculated on the pooled mortality incidences at each dose.
The LD50, 95% confidence limits, and slope were calculated from the logarithm of the doses and the incidences of mortality using a SAS PROBIT procedure (SAS Institute, Inc. SAS User's Guide: Statistics, Version 5 Edition, p 171-253. Cary, NC: SAS Institute Inc., 1985) based on the method of D.J. Finney (Probit Analysis, Third Edition, London: Cambridge University Press, 1971).
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
251 mg/kg bw
95% CL:
> 190 - < 322
Mortality:
- Time of death: Males - 1 at 200 mg/kg 4 hr post-dosing (day 0); 3 at 400 mg/kg 2 hr post-dosing (day 0); 3 at 400 mg/kg 4 hr post-dosing (day 0). Females - 1 at 200 mg/kg 4 hr post-dosing (day 0); 1 at 200 mg/kg on day 1; 5 at 400 mg/kg 4 hr post-dosing (day 0). A dose-related increase in mortality was observed in the 200- and 400-m/kg dose groups.
- Number of deaths at each dose: (number of deaths/number treated)
Dose (mg/kg) 50 200 400
Males 0/6 1/6 6/6
Females 0/6 2/6 5/6
Clinical signs:
No mortalities and no clinical signs related to the test substance were seen in the 50- mg/kg dose group. Clinical signs indicative of neurotoxicity (tremors and/or convulsions) were observed in survivors as well as decedents in the 200- and 400-mg/kg dose groups. Surviving animals recovered from the neurotoxic effects by day 1 of the study. Periodically during the study, the fur surrounding the eyes and muzzle was observed to be red-stained; these effects were judged to be caused by the occluded testing methodology and by the use of collars. Numerous skin irritation effects were seen in both sexes at all doses.
Body weight:
There was no apparent test substance related body weight effects in this study.
Gross pathology:
Necropsy of the decedents revealed numerous skin irritation effects related to the test substance. No gross changes observed in survivors.
Other findings:
- Potential target organs: skin
- Other observations: no statistically significant sex-related differences
Interpretation of results:
Category 3 based on GHS criteria
Executive summary:

The dermal toxicity of the test material was evaluated in Crl:CD BR rats. The test material was dispersed in neutral oil and applied topically to the shaved intact skin of three groups of rats (6/sex/group) at 50, 200 or 400 mg/kg (2 ml/kg) body weight. The application sittes were occluded for 24 hr. After the 24 -hr exposure, the application sites were washed with tap water. No mortalities and no clinical signs related to the test substance were seen in the 50 mg/kg dose group. A dose-related increase in mortality was observed in the 200 and 400 mg/kg dose groups. Clinnical signs indicative of neurotoxicity (tremors and/or convulsions) were observed in survivors as well as decedents in the 200 and 400 mg/kg dose groups. Surviving animals recovered from the neurotoxic effects in this study. There was no apparent test substance related body weight effects in thsi study. Numerous skin irritation effects were seen in both sexes at all doses. No treatment related signs were seen at necropsy (other than skin irritaion). The overall no observed effect level (NOEL) was 50 mg/kg.

Sincec no statistically significant sex-related difference in mortality was observed, the LD50 was calculated from the combined mortality incidence data. The acute dermal LD50 in male and female rats (combined) was 251 mg/kg with 95% confidence limits of 190 and 322 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
251 mg/kg bw

Additional information

The acute oral toxicity of the test material was evaluated in male and female Crl:CD BR rats by gavage. Since there was a statistically significant sex-related difference in mortality observed, the LD50 was calculated separately for males and females. The acute oral LD50 in male rats was 1177 mg/kg with 95% confidence limits of 974 and 1422 mg/kg. The acute oral LD50 in female rats was 612 mg/kg with 95% confidence limits of 442 and 848 mg/kg. The acute dermal toxicity of teh test material was evaluated in male and female Crl:CDBR rats. Since no statistically significant sex-related difference in mortality was observed, the LD50 was calculated from the combined mortality incidence data. The acute dermal LD50 in male and female rats (combined) was 251 mg/kg with 95% confidence limits of 190 and 322 mg/kg. Rats appear to be more sensitive than rabbits to acute dermal dosing of the test material.

The acute inhalation toxicity of the test material was assessed in Crl: CD Rats. The LC50 value was calculated from the female mortality incidence data. The acute inhalation LC50 for the test material in female rats was 157 ppm (1.19 mg/L) with 95% limits of 90 to 249 ppm. The acute inhalation LC50 for the test material in male rats was greater than 231 ppm (1.75 mg/L). 

The irritating effects of tissue contact with the test material were evident in studies by all exposure routes. Clinical signs indicative of acute neurotoxicity (e.g., abnormal gait, hyperactivity, tremors, convulsions, salivation, and ataxia) were observed in studies by all routes of exposure.

Justification for classification or non-classification

The acute oral toxicity classification is harmful based on an LD50 of 612 mg/kg in rats. The classification is toxic by the inhalation and dermal routes based on an acute dermal LD50 of 251 mg/kg and an acute inhalation LC50 of 1.19 mg/L under the EU criteria.

In consideration of an H335 classification of the test material, the acute rat inhalation study demonstrated that the toxicity was concentration dependant and elicited at the point of contact.  No further classification is needed based on the corrosive nature of the material.