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Administrative data

Description of key information

The key acute oral toxicity study is an OECD 401, GLP study in rats.

The key acute dermal toxicity study is an OECD 402, GLP study in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9/19/2001-10/3/2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
other: Japan 59 NohSan Notification No. 4200, Acute Oral Toxicity Study
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
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:
Adult male and female Crl:CDaBR rats were obtained from Charles River Laboratories, Raleigh, NC. Upon arrival, all animals were examined for physical abnormalities and quarantinedlacclimated for approximately one week. The animals were individually housed in suspended stainless steel cages (18x34x20cm) with wire mesh fronts and bottoms. Cages were suspended above absorbent-paper pan liners, which were changed 3 times a week. Throughout the test period, all rats had free access to water (via automatic watering) purified by reverse osmosis and PMI Certified Rodent Diet 5002(C) (Purina Mills Inc., Richmond, IN). The animal room was environmentally controlled with controls set to maintain a temperature of approximately 23°C and a relative humidity range of 30-70%. The temperature and relative humidity were monitored 24 hrs a day. During the study, the average daily temperature was approximately 22°C and the average daily relative humidity ranged from 44 to 54%. Any excursions beyond these ranges were minimal and did not affect the integrity of the study. Temperature and relative humidity remained in compliance with acceptable ranges defined in the "Guide for the Care and Use of Laboratory Animals" ISBN No. 0-309-05377-3, Revised 1996. The light cycle was automatically controlled, 12 hrs on and 12 hrs off.

Prior to treatment, rats were selected from a healthy stock population, assigned to the study group using a computer-generated sequence of random numbers, identified by uniquely numbered ear tags, and fasted overnight. At the time they were dosed, the males were approximately 8 weeks old and the females were approximately 9 weeks old. The fasted body weights ranged from 208 to 242 g for males and from 182 to 201 g for females.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The undiluted test substance was was administered to male and female rats at 250, 750 or 1250 mgkg body weight. Dose was calculated on an "as is" basis; no adjustment was made for percent active ingredient. No analytical verification of the dosing solution was performed since the test substance was administered undiluted.
Doses:
250, 750, and 1250 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
All animals were observed for signs of ill health, or reaction to treatment at approximately 1,2 and 4 hrs after dosing and once daily thereafter for 14 days. Body weights were recorded on day 0 (prior to dosing) and on days 7 and 14. Decedents were necropsied as they were found. Surviving rats were euthanized on day 14 and necropsied. Necropsy consisted of a gross examination of organs in situ.
Statistics:
The mortality incidences of males and females were compared across doses with a categorical data modeling procedure using SAS CATMOD (SAS Institute Inc. SAS User's Guide: Statistics, Version 6 Edition, p 405-517. Cary, NC: SAS Institute Inc., 1990). The criterion of statistical significance was 0.05. Since the results did not indicate a significant difference between the mortality responses across dose groups for males and females, the LD50 was calculated on the pooled (male and female combined data) mortality incidences at each dose.

The LD5o 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, Third Edition, London: Cambridge University Press, 1971). The procedure was unable to determine the 95% confidence limits.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
763 mg/kg bw
Based on:
test mat.
Mortality:
Two male and 2 female animals at 750 mg/kg died by day 3 and all rats at 1250 mg/kg died by day 1.
Clinical signs:
No clinical signs of toxicity were noted in males at 250 mglkg during the 14-day observation period. Scant feces was noted in females at 250 mglkg on day 1 only. Numerous clinical signs of toxicity were noted in males and/or females at 750 and/or 1250 mg/kg. These included: soft, scantlno feces, red or tan stained muzzle, passiveness, ataxia, yellow/brown stained anogenital area, and red-stained eyes. These clinical signs were evident beginning on day 0 and continued through day 5.

Respiratory noise noted in several animals was probably due to some of the test substance being aspirated during dosing. Gasping or labored breathing was judged to be due to the dosing material being aspirated or was considered agonal. In addition, other clinical signs considered agonal at 750 or 1250 mglkg included: cyanotic, prostration, dilated pupil, lacrimation, hunched posture and salivation.
Body weight:
Body weight gain among swvivors in both sexes at 750 mg/kg was decreased (32-39%) when compared to historical control values. There was no treatment-related effect on body weight gain among both sexes at 250 mg/kg.
However, all surviving animals gained weight by the end of the observation period.
Gross pathology:
Necropsy of the decedents in both sexes at 750 and 1250 mg/kg revealed numerous gastrointestinal changes. These included: stomach: distended, thickened, contains clear fluid, glandular portion reddened and/or sloughing, contains gelatinous material and intestine reddened. Carcass autolysis was also noted. Necropsy of the survivors at 250 mg/kg (both sexes) and 750 mg/kg (males) revealed no gross changes. One female survivor at 750 mg/kg was found with stomach wall thickened.
Other findings:
The acute oral LD50 in male and female rats was 763 mg/kg. The log probit slope of the dose-mortality data (probit incidence versus log dose) was 7.72 in this study.

Table 1. Mortality

 Dose (mg/kg)  250  750  1250
 Males  0/5  2/5  5/5
 Females  0/5  2/5  5/5
 Combined sexes  0/10  4/10  10/10
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral LD50 for OXEMA in male and female rats was 763 mg/kg bw.
Executive summary:

The acute oral toxicity of Monomer OXEMA was assessed in Crl: CD®BR rats. Three groups of five male and five female rats/groups were gavaged with the test substance, as received, at 250,750 or 1250 mg/kg body weight. Two male and 2 female animals at 750 mg/kg died by day 3 and all rats at 1250 mg/kg died by day 1. No clinical signs of toxicity were noted in males at 250 mg/kg during the 14-day observation period. Scant feces were noted in females at 250 mg/kg on day 1 only. Numerous clinical signs of toxicity were noted in males and/or females at

750 and/or 1250 mg/kg. These included: soft, scant/no feces, red or tan stained muzzle, passiveness, ataxia, yellow/brown stained anogenital area, and red-stained eyes. These clinical signs were evident beginning on day 0 and continued through day 5. Body weight gain among survivors in both sexes at 750 mg/kg was decreased (32-39%) when compared to historical control values. There was no treatment related effect on body weight gain among both sexes at 250 mg/kg. Necropsy of the decedents in both sexes at 750 and 1250 mg/kg revealed numerous gastrointestinal changes. Necropsy of the survivors at 250 mg/kg (both sexes) and 750 mg/kg (males) revealed no gross changes. One female survivor at 750 mg/kg was found with stomach wall thickened. The acute oral LD50 for OXEMA in male and female rats was 763 mg/kg.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
pre-GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Clinical observations made only on Days 1, 2, 3, 5, 7, and 14; Body weights not recorded.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Initial body weights ranged from 145 to 198 grams for the males and from 140 to 173 grams for the females, and the animals were fasted overnight prior to dosing.
Route of administration:
oral: gavage
Vehicle:
water
Doses:
215, 364, 1000, 2150, 3640 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
Observations for mortality and signs of effects were made immediately after dosing; at one, four, and 24 hours; and on Days 2, 3, 5, 7, and 14. Gross necropsy was performed on all animals which died during the study and on all surviving animals at terminal sacrifice (exsanguination following chloroform overdose).
Statistics:
Mortality data were analyzed statistically by the method of Litchfield, J.T., and Wilcoxon, F., J. Pharmacol. Exptl. Therap. 96, 99, 1949.
Sex:
male
Dose descriptor:
LD50
Effect level:
863 mg/kg bw
Based on:
test mat.
95% CL:
ca. 507 - ca. 1 469
Sex:
female
Dose descriptor:
LD50
Effect level:
603 mg/kg bw
Based on:
test mat.
95% CL:
ca. 397 - ca. 916
Mortality:
Males: Death occurred immediately after dosing in all 3640 mg/kg bw exposed males and in 4/5 2150 mg/kg bw exposed males. The 5th 2150 mg/kg bw exposed male died within 1-4 hours from exposure. 3/5 1000 mg/kg bw exposed males died within 24 hours. All 215 and 364 mg/kg bw exposed males survived the 14 day observation period, as did 2 1000 mg/kg bw exposed males.

Females: All 2150 and 3640 mg/kg bw exposed females died immediately after dosing. All 1000 mg/kg bw exposed females died - 3 within 1 hour of dosing, 1 within 4 hours of dosing, and 1 within 24 hours of dosing. All 215 and 364 mg/kg bw exposed animals survived the 14 day observation period.
Clinical signs:
No toxic effects were observed in 215 and 364 mg/kg bw males of females. At the 1000 mg/kg bw dose level, depression was observed immediately post-dose. Signs noted at 1 and 4 hours included depression, ataxia, and/or labored respiration. The 2 males surviving at this dose level appeared normal from 24 hours throughout the remainder of the study. Convulsions and prostration preceded death at the 2150 and 3640 mg/kg bw dose levels.
Gross pathology:
No gross abnormalities were observed at death or at terminal sacrifice for either sex.

Table 1: Male Mortality

Dose (mg/kg)

Concentration (% vol/vol)

Cumulative Mortality - Males

Immediate

1-4 Hours

24 Hours

2-14 Days

215

10

0/5

0/5

0/5

0/5

364

10

0/5

0/5

0/5

0/5

1000

Undiluted

0/5

0/5

3/5

3/5

2150

Undiluted

4/5

5/5

--

--

3640

Undiluted

5/5

--

--

--

LD50: 863 mg/kg

Confidence Limits (95%): 507 -1469 mg/kg

Slope: 1.994

Table 2: Female Mortality

Dose (mg/kg)

Concentration (% vol/vol)

Cumulative Mortality - Females

Immediate

1 Hour

4 Hours

24 Hours

2-14 Days

215

10

0/5

0/5

0/5

0/5

0/5

364

10

0/5

0/5

0/5

0/5

0/5

1000

Undiluted

0/5

3/5

4/5

5/5

--

2150

Undiluted

5/5

--

--

--

--

3640

Undiluted

5/5

--

--

--

--

LD50: 603 mg/kg

Confidence Limits (95%): 397-916 mg/kg

Slope: 1.483

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
OXEMA was evaluated for acute oral toxicity by oral intubation to five groups of five male and five female adult albino rats. Dosage levels were 215, 364, 1000, 2150, and 3640 mg/kg bw. The animals were observed for mortality and toxic effects for a post-dose period of 14 days. The calculated LD50s were 863 mg/kg bw for males (95% CI: 507 -1469) and 603 mg/kg bw for females (95% CI: 397 -916).
Executive summary:

OXEMA was evaluated for acute oral toxicity by oral intubation to five groups of five male and five female adult albino rats. Dosage levels were 215, 364, 1000, 2150, and 3640 mg/kg bw. The animals were observed for mortality and toxic effects for a post-dose period of 14 days. The calculated LD50s were 863 mg/kg bw for males (95% CI: 507 -1469) and 603 mg/kg bw for females (95% CI: 397 -916).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
763 mg/kg bw
Quality of whole database:
Guideline/GLP study available.

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
Study period:
9/19/2001-10/16/2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
other: Japan 59 NohSan Notification No. 4200, Acute Dermal Toxicity Study
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:
Adult male and female Crl:CD®BR rats were obtained from Charles River Laboratories, Raleigh, NC. Upon arrival, all animals were examined for physical abnormalities and quarantined/acclimated for approximately one week. The animals were individually housed in suspended stainless steel cages (18x34x20 cm) with wire mesh fronts and bottoms. Cages were suspended above absorbent-paper pan liners, which were changed 3 times a week. Throughout the test period, all rats had free access to water (via automatic watering) purified by reverse osmosis and PMI Certified Rodent Diet 5002(C) (Purina Mills Inc., Richmond, IN). The animal room was environmentally controlled with controls set to maintain a temperature of approximately 23 °C and a relative humidity range of 30-70%. The temperature and relative humidity were monitored 24 hrs a day. During the study, the average daily temperature was approximately 22°C and average daily relative humidity ranged from 44 to 54%. Any excursions beyond these ranges were minimal and did not affect the integrity of the study. Temperature and relative humidity remained in compliance with acceptable ranges defined in the "Guide for the Care and Use of Laboratory Animals" ISBN No. 0-309-05377-3, Revised 1996. The light cycle was automatically controlled, 12 hrs on and 12 hrs off.

On the day prior to treatment, rats were selected from a healthy stock population, assigned to the study group using a computer-generated sequence of random numbers and identified by uniquely numbered ear tags. At the time they were dosed, the males were approximately 8 weeks old and the females were approximately 9 weeks old. The body weights ranged from 236 to 274 g for males and from 204 to 244 g for females.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hrs prior to the application of the test substance, the hair around the entire trunk between the flank and shoulders was shaved closely with electric clippers. The test substance, undiluted, was applied topically to the shaved intact skin (target of 10% body surface area) of five male and five female rats at 2000, 1200 or 400 mg/kg body weight. Dose was calculated on an "as is" basis; no adjustment was made for percent active ingredient. The entire trunk of each animal was wrapped in a polyethylene sheet covered with Elastoplast® (Beiersdorf, Inc., Norwalk, CT) and PEG®(Becton-Dickinson Co., Franklin Lakes, NJ) elastic bandages and secured in place with adhesive tape.

The test substance remained in contact on the skin of each animal for 24 hrs. Each cuff was removed after the 24-hr exposure period, and the application site was wiped with paper towels saturated with tap water. The application site was blotted dry with paper towels, and the approximate dimensions of the contact area of the test substance were determined.

Each animal was fitted with a cardboard collar to prevent preening of the application site. The collar was worn throughout the 14-day observation period.

After dermal application, the test substance covered an area approximately 6 cm x 6 cm.
Duration of exposure:
24
Doses:
400, 1200, 2000 mg/kg
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
All animals were observed for signs of ill health, or reaction to treatment at approximately 1, 2 and 4 hrs after dosing and once daily thereafter for 14 days. Body weights were recorded on day 0 (prior to dosing) and on days 7 and 14.

Decedents were necropsied as they were found. Surviving rats were euthanized on day 14 and necropsied. Necropsy consisted of a gross examination of organs in situ.
Statistics:
The mortality incidences of males and females were compared across doses with a categorical data modeling procedure using SAS CATMOD (SAS Institute Inc. SAS User's Guide: Statistics, Version 6 Edition, p 405-517. Cary, NC: SAS Institute Inc., 1990). The criterion of statistical significance was 0.05. Since the results did not indicate a significant difference between the mortality responses across dose groups for males and females, the LDso was calculated on the pooled (male and female combined data) 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 PR OBIT 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, Third Edition, London: Cambridge University Press, 1971 ).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 641 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 115 - ca. 3 663
Mortality:
Three males and 4 females at 2000 mg/kg and 2 females at 1200 mg/kg died by day 2. No deaths occurred in either sex at 400 mg/kg.
Clinical signs:
Scant or no feces was observed in both sexes at 2000 mg/kg on days 1 and 2. Ataxia and passiveness were seen in both sexes at 2000 mg/kg and in one female at 1200 mg/kg on day 1. There were no clinical signs of systemic toxicity noted in either sex at 400 or in males at 1200 mg/kg.

Periodically during the study, the fur surrounding the eyes and muzzle of several animals was observed to be red stained; these effects were judged to be caused by the occluded testing methodology and by the use of collars.

Skin effects, (i.e., edema,. erythema, pocketing edema, eschar, blanching, dark areas, scabs, sloughing and desiccation), were observed in both sexes at all levels beginning on day 1 and continued through the day 14 observation period.
Body weight:
Body weight gain over the 14-day observation period was decreased (10- 71 %) in both sexes at all levels when compared to historical control data.
However, all surviving animals gained weight by the end of the observation period.
Gross pathology:
Necropsy of the decedents in both sexes at 2000 mg/kg revealed carcass autolysis and gastrointestinal changes which included stomach: contains black material, glandular portion reddened, and intestine: reddened or blackened. Two females at 1200 mg/kg revealed carcass autolysis only. Necropsy of survivors revealed no gross observations.
Other findings:
The acute dermal LD50 in male and female rats is 1641 mg/kg with 95% confidence limits of 1115 to 3 663. The log probit slope of the dose-mortality data (probit incidence versus log dose) was 4.89 in this study.

Table 1: Male Mortality

 Dose (mg/kg bw)  Died  Comments
 400  0/5  
 1200  0/5  
 2000  3/5

 All died on day 1.

Table 2: Female Mortality

 Dose (mg/kg bw)  Died  Comments
 400  0/5  
 1200  2/5  Animals died on days 1 and 2.
 2000  4/5  Animals died on days 1 (n=3) and 2 (n=1).
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute dermal toxicity of OXEMA was assessed in Crl:CD®BR rats. The test substance was applied to the shaved intact skin of five male and five female rats at 2000, 1200 or 400 mg/kg body weight. The application sites were occluded for 24 hrs. After the 24-hr exposure, the application sites were wiped with paper towels saturated with tap water and blotted dry with paper towels.

Three males and four females died at 2000 mg/kg and two females died at 1200 mg/kg. Scant or no feces was noted in both sexes on days 1 and 2. Ataxia and passiveness were seen in both sexes at 2000 mg/kg and in one female at 1200 mg/kg on day 1. There were no clinical signs of systemic toxicity noted in either sex at 400 or in males at 1200 mg/kg. Signs of skin irritation (i.e., edema, erythema, pocketing edema, eschar, blanching, dark areas, scabs, sloughing and desiccation) were observed in both sexes at all levels beginning on day 1 and continued through the day 14 observation period. Body weight gain over the 14-day observation period was decreased (10-71 %) in both sexes at all levels when compared to historical control data. Necropsy of the decedents in both sexes at 2000 mg/kg revealed gastrointestinal changes. Necropsy of decedents at 1200 mg/kg showed no treatment-related changes. Necropsy of survivors revealed no gross observations. The acute dermal LD50 in male and female rats for OXEMA is 1641 mg/kg with 95% confidence limits of 1115 to 3663.
Executive summary:

The acute dermal toxicity of OXEMA was assessed in Crl:CD®BR rats. The test substance was applied to the shaved intact skin of five male and five female rats at 2000, 1200 or 400 mg/kg body weight. The application sites were occluded for 24 hrs. After the 24-hr exposure, the application sites were wiped with paper towels saturated with tap water and blotted dry with paper towels.

Three males and four females died at 2000 mg/kg and two females died at 1200 mg/kg. Scant or no feces was noted in both sexes on days 1 and 2. Ataxia and passiveness were seen in both sexes at 2000 mg/kg and in one female at 1200 mg/kg on day 1. There were no clinical signs of systemic toxicity noted in either sex at 400 or in males at 1200 mg/kg. Signs of skin irritation (i.e., edema, erythema, pocketing edema, eschar, blanching, dark areas, scabs, sloughing and desiccation) were observed in both sexes at all levels beginning on day 1 and continued through the day 14 observation period. Body weight gain over the 14-day observation period was decreased (10-71 %) in both sexes at all levels when compared to historical control data. Necropsy of the decedents in both sexes at 2000 mg/kg revealed gastrointestinal changes. Necropsy of decedents at 1200 mg/kg showed no treatment-related changes. Necropsy of survivors revealed no gross observations. The acute dermal LD50 in male and female rats for OXEMA is 1641 mg/kg with 95% confidence limits of 1115 to 3663.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 641 mg/kg bw
Quality of whole database:
Guideline/GLP study available.

Additional information

Acute Oral Toxicity

In the key study, groups of five male and five female Crl:CD BR rats were exposed to undiluted OXEMA at doses of 250, 750, or 1250 mg/kg bw by oral gavage. Two male and two female animals at 750 mg/kg bw died by day 3 and all rats at 1250 mg/kg bw died by day 1. No clinical signs were noted in 250 mg/kg bw exposed males at any time during the 14 day observation period. Scant feces were noted in 250 mg/kg bw exposed females on day 1 only. Males and females exposed to 750 or 1250 mg/kg bw showed the following signs of toxicity from days 0 through 5: soft, scant/no feces, red or tan stained muzzle, passiveness, ataxia, yellow/brown stained anogenital area, and red-stained eyes. Body weight gain was decreased (32 -30%) in 750 mg/kg bw exposed males and females when compared to historical controls. Body weights were unaffected at 250 mg/kg bw. Gastrointestinal changes were observed in decedents of both sexes. No gross changes were observed in survivors, with the exception of one female survivor at 750 mg/kg bw who was found with stomach wall thickened. The acute oral LD50 for OXEMA in male and female rats was 763 mg/kg bw.

In a supporting study, groups of five male and five female Sprague-Dawley rats received doses of 215, 364, 1000, 2150, or 3640 mg/kg bw by oral intubation. All animals exposed to 2150 and 3640 mg/kg bw died within 4 hours of exposure; deaths were preceded by convulsions and prostration. All females and 3/5 males exposed to 1000 mg/kg bw died within 24 hours of exposure. In 1000 mg/kg bw exposed animals, depression, ataxia, and labored respiration was observed. Surviving males at this dose level appeared normal from 24 hours through the end of the study. No signs of toxicity were observed in 215 and 364 mg/kg bw exposed males or females. No gross abnormalities were observed at death or sacrifice for either sex. The LD50 was 863 mg/kg bw for males and 603 mg/kg bw for females.

Acute Dermal Toxicity

Undiluted OXEMA was applied to the shaved intact skin of five male and five female rats/group at 400, 1200, or 2000 mg/kg bw for 24 hours under occluded conditions. Three males and four females died at the 2000 mg/kg bw dose died within 2 days and two females died at the 1200 mg/kg bw dose. Scant or no feces was noted in both sexes on days 1 and 2. Ataxia and passiveness were seen in both sexes at 2000 mg/kg and in one female at 1200 mg/kg on day 1. There were no clinical signs of systemic toxicity noted in either sex at 400 or in males at 1200 mg/kg. Signs of skin irritation (edema, erythema, pocketing edema, eschar, blanching, dark area, scabs, sloughing, and desiccation) were observed in both sexes at all levels beginning on day 1 and continued through the 14 day observation period. Body weight gain over the 14 day observation period was decreased (10 -71%) in both sexes at all levels when compared to historical control data. Necropsy of the decedents in both sexes at 2000 mg/kg revealed gastrointestinal changes. No treatment related changes were observed in 1200 mg/kg bw decedents or in survivors at any dose level. The acute dermal LD50 in male and female rats for OXEMA is 1641 mg/kg, suggesting that OXEMA is not absorbed through the skin in toxicologically significant amounts.

Justification for classification or non-classification

Acute Oral Toxicity

The acute oral LD50 of OXEMA is 763 mg/kg bw, warranting Category IV Classification for acute oral toxicity according to GHS.

Acute Dermal Toxicity

The acute dermal LD50 of OXEMA is 1641 mg/kg bw, warranting Category IV Classification for acute dermal toxicity according to GHS.