Hexanoic acid, 3,5,5-trimethyl-, tin(2+) salt (2:1)

Endpoint summary

Description of key information

The oral LD50 male/female in rats was determined to be > 300 - 2000 mg/kg bw in an acute oral toxicity study, Acute Toxic Class Method according to OECD guideline 423. The dermal LD50 male/female in rats was determined to be > 2000 mg/kg bw in an acute dermal toxicity study according to OECD guideline 402.

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

Study period:

2010-11-29 to 2010-12-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 10 weeks at delivery, approx. 11 weeks at day of application
- Weight at study initiation: 202.2 ± 5.8 g (dose group 300 mg/kg) and 207.7 ± 5.9 g (dose group 2000 mg/kg) at day of application
- Fasting period before study: overnight before application
- Housing: Three rats were housed in one Makrolon cage type IV
- Diet (e.g. ad libitum): ad libitum, Altromin Rats/mice maintenance diet 1324
- Water (e.g. ad libitum): ad libitum, tap water from municipal source
- Acclimation period: 6 to 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours dimmed light, 12 hours dark

IN-LIFE DATES: From: 2010-11-23 To: 2010-12-15

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 % w/w for the 300 mg/kg bw and undiluted for the 2000 mg/kg bw dose
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required): Lot 068K0150

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6 females per dose, in a stepweise procedure

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: immediately, 1 hour and 3 hours after test substance administration and thereafter daily
except on one Saturday and one Sunday in the second week p.a.; weighing: before dosing , after 7 days and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

300 mg/kg bw - no animal died
2000 mg/kg bw - in the first step no animal died, but in the second step two of the three animals died

Clinical signs:

other: 300 mg/kg bw - no symptoms of toxicity 2000 mg/kg bw : Two animals showed symptoms of toxicity like reduced activity and ventral position. 20 h p.a one of the two animals was found dead; the second one was found morbund (unconscious and with reduced resp

Gross pathology:

The necropsy 14 days after oral application showed no test substance related macroscopic visible pathologic organ findings in the survived animals.
The necropsy of the sacrificed animal 20 h p.a. revealed that the liver was discolored yellowish. No necropsy was performed on the animal found
dead
due to advanced maceration.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The LD50-value for acute oral toxicity of the test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) is > 300 - 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study performed according to the OECD Guideline 423, (Acute Toxic Class Method, 2001), 6 female 10 weeks old HanRcc:WIST (SPF) rats per group were given a single oral dose of test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1)

, in sesame oil at doses of 300 and 2000 mg/kg bw and observed for 14 days.The test substance was applied as 10 % (w/w) preparation in vehicle and undiluted.

 

The test substance was tolerated by the test animals at a dose of 300 mg/kg body weight without any symptoms of toxicity. A dose of 2000 mg/kg body weight caused symptoms of toxicity (reduced activity and cower position) in four of six animals and two of these animals died within 20 h following oral administration of the test substance. Body weight development was not negatively affected in all animals that survived.

 

According to the test procedure scheme given in the test guideline the LD₅₀-value for acute oral toxicity of the test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) is > 300 - 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

Data from a GLP compliant guideline study with reliability 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no 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:

2011-04-04- to 2011-04-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: White Wistar, HsdCpb: WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 7 weeks at delivery, approx. 8 weeks at day of application
- Weight at study initiation: 186.2 ± 8.4 g (female) and 213.9 ± 6.7 (male) at day of application
- Housing: One rat was housed in a Makrolon cage type III
- Diet (e.g. ad libitum): ad libitum, Altromin Rats/mice maintenance diet 1324
- Water (e.g. ad libitum): ad libitum, tap water from municipal source
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours dimmed light, 12 hours dark

IN-LIFE DATES: From: 2010-11-23 To: 2010-12-15

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10 %
- Type of wrap if used:
The test substance was applied uniformly over the test site (approx. 10 % of the body surface area), covered with a gauze pad (4 x 5 em, Brauncel, B. Braun Petzold GmbH, Melsungen, Germany) which was held in place by strips of Micropore (3M company, St. Paul, USA). The dressing was bandaged with Acrylastic (Beiersdorf AG, Hamburg, Germany) and fixed with Leukoplast (Beiersdorf AG, Hamburg, Germany).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (Density 1.19 g/cm³)
- Concentration (if solution): undiluted


VEHICLE
- Amount(s) applied (volume or weight with unit): undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical examination was performed immediately, 1 hour and 4 hours after test substance administration and thereafter daily except on Saturdays and Sundays. Determination of body weights took place before dosing, after 7 days and 14 days.

- Necropsy of survivors performed: yes;
After completion the test animals were sacrificed with carbon dioxide and necropsied.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: no animal died

Mortality:

All animals survived until the termination of the experiment 14 days p.a.

Clinical signs:

other: No signs of irritation or other clinical signs were observed.

Gross pathology:

The necropsy of all animals 14 days after application showed no macroscopic visible test substance related pathologic organ findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The LD50-value for acute dermal toxicity of the test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) is > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, 1987 and EU method B.3, 5 male and 5 female young adult white Wistar rats were dermally exposed to the hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) for 24 hours under an occlusive dressing to approx. 10 % of body surface area at doses of 2000 mg/kg bw. Animals then were observed for14 days.

 

Dermal LD₅₀            Males:             > 2000 mg/kg bw

                                 Females:          > 2000 mg/kg bw

                                 Combined:      > 2000 mg/kg bw

 

No mortality occurred in this limit test.

 

No signs of skin irritation were observed at the site of application. Symptoms of systemic toxicity or unusual findings were not recorded at any time during the study. Weight gain was positive within normal range. No macrospic visible substance related pathologic organ findings were noted at terminal necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data from a GLP compliant guideline study with reliability 1.

Additional information

Acute toxicity oral:

In an acute oral toxicity study performed according to the OECD Guideline 423, (Acute Toxic Class Method, 2001), 6 female 10 weeks old HanRcc:WIST (SPF) rats per group were given a single oral dose of test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1), in sesame oil at doses of 300 and 2000 mg/kg bw. Animals then were observed for14 days. The test substance was applied as 10 % (w/w) preparation in vehicle and undiluted.

The test substance was tolerated by the test animals at a dose of 300 mg/kg body weight without any symptoms of toxicity. A further group of six female rats were dosed with 2000 mg test substance/kg body weight in a stepwise procedure, each step using three animals. In the first step no mortality occurred, but in the second step two of the three animals died.

Symptoms of toxicity (reduced activity and cower position) were observed in four of six animals receiving 2000 mg/kg bw and two of these animals died within 20 h following oral administration of the test substance. Body weight development was not negatively affected in all animals that survived.

The LD₅₀ for the test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) was determined to be > 300 - 2000 mg/kg body weight.

 

Acute toxicity dermal:

In an acute dermal toxicity study according to OECD guideline 402, 1987, 5 male and 5 female young adult white Wistar rats were dermally exposed to the hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) for 24 hours under an occlusive dressing to approx. 10 % of body surface area at doses of 2000 mg/kg bw. Animals then were observed for14 days.

No mortality occurred in this limit test. No signs of skin irritation were observed at the site of application. Symptoms of systemic toxicity or unusual findings were not recorded at any time during the study. Weight gain was positive within normal range. No macroscopically visible substance related pathologic organ findings were noted at terminal necropsy.

The dermal LD₅₀ male/female in rats was determined to be > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Data from a GLP compliant guideline study with reliability 1.

Justification for selection of acute toxicity – dermal endpoint
Data from a GLP compliant guideline study with reliability 1.

Justification for classification or non-classification

Data from an acute oral toxicity study using the Acute Tox Class Method according to OECD guideline 423 are available. According to the CLP (EU-GHS) Regulation (EC) No1272/2008 the test substance has to be classified with category IV for acute oral toxicity and with R22 according to Directive 67/548/EEC, respectively.

 

Based on the dermal LD₅₀of > 2000 mg/kg bw a non-classification for acute dermal toxicity is justified according to CLP (EU-GHS) Regulation (EC) No1272/2008 and Directive 67/548/EEC.