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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Aliquat 175
- Physical state: clear liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: MJV59-115-1

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: at least 12 weeks
- Weight at study initiation: between 2.01 - 2.55 kg
- Housing: individually in stainless steel cages
- Diet: Purina Rabbit Chow, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 30-70

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the dorsal and ventral areas of the trunks of the rabbits were shaved (electric clippers), the areas shaved were approximately 30% of the total body surface area
- % coverage: approx. 10
- Type of wrap if used: Two layers of porous gauze dressing and a sleeve of plastic sheeting was fitted over the shaven trunk of the animal and secured in place with non-irritating surgical tape.

REMOVAL OF TEST SUBSTANCE
- Washing: remaining test article wiped off
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 and 200 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed frequently during the day of dosing and once daily for 14 days following dosing. The weight of each animal was determined prior to dosing, and for survivors at 7 days and at the end of the 14 days.
- Necropsy of survivors performed: yes
Statistics:
At the end of the observation period, calculations of the LD50 and 95% confidence limits are performed, if necessary, by the method of moving averages, using the tables constructed by Weil, (Weil C.C.: Table for Convenient Calculations of Median Effective Dose (LD50 and ED50) and lnstruction in Their use). Biometrics, 8, 249 (1952).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 851.928 - <= 2 159.911
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 500 mg/kg bw
Based on:
act. ingr.
95% CL:
>= 1 388.925 - <= 1 619.933
Remarks on result:
other: Aliquat 175 consists of ca. 75 % tributylmethylammonium chloride (56375-79-2) and ca. 25 % water
Mortality:
At the 2000 mg/kg body weight level, 50% mortality occurred during the 14 day observation period. At the 200 mg/kg body weight level, no mortality occurred during the 14 day observation period.
Clinical signs:
At the 2000 mg/kg bw dose level, all animals were extremely hyperactive (excessive jumping and thrashing about in the cage) immediately following dosing. Most likely indicative of discomfort from application of the test material. Additionally, edema at the application site was observed from day 1 to day 4 and erythema at the application site was observed from day 1 to day 6. Eschar formation at the application site was observed from day 5 until the end of the observation period.
Clinical signs observed in the 200 mg/kg dose group were normal. From day 1 to day 3, edema was observed at the application site. Additionally, erythema was observed on day 1 and 2.
Body weight:
See: " Any other information on results incl. tables"
Gross pathology:
There were no internal or external changes found in the 200 mg/kg dose group. In the 2000 mg/kg dose group no gross changes were found however, some minor effects were observed. For details see the table in: " Any other information on results incl. tables"

Any other information on results incl. tables

Table 1: Body weight and clinical signs

DOSE group 2000 mg/kg  

RABBIT

SEX Initial BWT Dose  7 DAY BWT 14 DAY BWT   FATE  FINDINGS
 (kg) (grams)  (kg)  (kg)  
546 M 2.25 4.50 --- --- Day of dosing External: No gross changes observed. InternaL: Stomach slightly distended with gas, no other gross changes observed.
547 M 2.30 4.60 2.34 2.52 Survived External: Eschar at the application site, no other gross changes observed.Internal: No gross changes observed.
548 M 2.36 4.72 --- --- Day of dosing External: No gross changes observed.Internal: No gross changes observed.
549 M 2.32 4.64 2.39 2.65 Survived External: Eschar at the application site, no other gross changes observed.Internal: No gross changes observed.
550 M 2.51 5.02 --- --- Day of dosing External: No gross changes observed.Internal: No gross changes observed.
551 F 2.42 4.84 --- --- day 1 External: Erythema and edema present at theapplication site, no other gross changes observed.Internal: Stomach slightly distended with gas, no other gross changes observed.
552 F 2.55 5.10 --- --- Day of dosing External: No gross changes observed.Internal: Liver appeared mottled, no gross changes observed.
553 F 2.32 4.64 2.20 2.33 Survived External: Eschar at the application site, no other gross changes observed.Internal: No gross changes observed.
554 F 2.10 4.20 1.96 2.16 Survived External: Eschar at the application site, no other gross changes observed.Internal: No gross changes observed.
555 F 2.01 4.02 1.82 1.97 Survived External: Eschar at the application site, no other gross changes observed.Internal: No gross changes observed.

Table 2: Body weight and clinical signs

DOSE group 200 mg/kg  
RABBIT SEX Initial BWT Dose  7 DAY BWT 14 DAY BWT  FATE   FINDINGS
 (kg) (grams)  (kg)  (kg)  
594 F 2.10 0.42 2.29 2.53 Survived External: No gross changes observed.Internal: No gross changes observed.
595 F 2.21 0.44 2.43 2.60 Survived  " "
596 F 2.24 0.45 2.42 2.58 Survived  " "
597 F 2.11 0.42 2.34 2.36 Survived  " "
598 F 2.29 0.46 2.41 2.47 Survived  " "
601 M 2.23 0.45 2.41 2.49 Survived  " "
602 M 2.22 0.44 2.38 2.43 Survived  " " 
603 M 2.10 0.42 2.26 2.43 Survived  " " 
604 M 2.25 0.45 2.39 2.52 Survived  " " 
605 M 2.47 0.49 2.63 2.75 Survived  " " 

Probitanalysis according to Finney including the 1000 mg/kg dose level of the second study:

Males

Dose: Number: Number survivors:

200 5 5

1000 5 5

2000 5 2

LD50 95% KI (lower) 95% KI (upper)

--------- -------------- --------------

1952.133 1755.310 2171.025

Intercept Slope

--------- ---------

-79.24 10.458

Goodness-of-Fit - Test (Pearson Chi-Square)

p-value

---------

1.0000

Females

Dose: Number: Number survivors:

200 5 5

1000 5 5

2000 5 3

LD50 95% KI (lower) 95% KI (upper)

--------- -------------- --------------

2052.734 1831.243 2301.015

Intercept Slope

--------- ---------

-74.24 9.735

Goodness-of-Fit - Test (Pearson Chi-Square)

p-value

---------

1.0000

Males and Females

Dose: Number: Number survivors:

200 10 10

1000 10 10

2000 10 5

LD50 95% KI (lower) 95% KI (upper)

--------- -------------- --------------

2000.000 1851.928 2159.911

Intercept Slope

--------- ---------

-76.76 10.099

Goodness-of-Fit - Test (Pearson Chi-Square)

p-value

---------

1.0000

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on an acute dermal toxicity study performed with MTBAC according to OPPTS 870.1200 guideline and GLP principles, it is concluded that the LD50 of MTBAC exceeds 2000 mg/kg bw/day. Corrected for the purity the LD50 for acute dermal exposure is ca. 1500 mg/kg bw.
Executive summary:

In an OPPTS 870.1200 guideline study, rabbits were treated with 200 and 2000 mg/kg bw. The test substance was applied dermally under occlusive conditions for 24 hours. No mortality occurred in the 200 mg/kg bw dose group however, 5 out of 10 animals died in the 2000 mg/kg bw dose group. Erythema, edema and eschar formation were observed during the observation period in the 2000 mg/kg bw dose group. In animals of the 200 mg/kg bw dose group edema and erythema were observed during day 1 to 3. No effects were observed after necropsy. The LD50 for acute dermal exposure is ca. 2000 mg/kg bw in the rabbit. The test item consists of ca. 75 % tributylmethylammonium chloride and ca. 25 % water. Corrected for the purity the LD50 for acute dermal exposure is ca. 1500 mg/kg bw.