Sodium 3-(allyloxy)-2-hydroxypropanesulphonate

Endpoint summary

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:

17 July 2012 - 13. September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Environmental conditions
Healthy femal rats were housed by group of three in solid bottomed clear polycarbonates cages.
Temperature 19 - 25° C
Relative humidity 30 - 70 %

Food and drinking
Drinking water and foodstuff were supplied freely. Food was removed on D-1 and then redistributed 4 hours after the test item administration.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

300 mg/kg bw/day and 2000 mg/kg bw/day

No. of animals per sex per dose:

6 rats (female) per dose

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured in animals dosed at 300 mg/kg bw and 2000 mg/kg bw.

Clinical signs:

other: Dose: 300 mg/kg bw No clinical signs related to the adminsitration of the test item were observed during the study. Dose: 2000 mg/kg bw A decrease in spontaneous activity (3/) and piloerection (3/6) were noted at 1 hour post-dose.

Gross pathology:

The macroscopic examination of the animal at the end of the study did not reveal treatment related changes.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD 50 of the test item is higer than 2000 mg/kg body weight by oral route in the rat.
In accordance with the OECD guideline No. 423, the LD50 cut off-of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat.
According to the criteria of classification , packaging and labelling of dangerous substances and preparation in accordance with the ECC Directives 67/548, 2001/59 and 99/45, the test item does not have to be classified. No symbol or risk phrase is required.
In accordance with the regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, the test item does not have to be classified. No signal word or hazard satement is requird.

Executive summary:

The test item was administrated to a group of 6 female Sprague Dawley rats at a single dose of 300 mg/kg body weight ans then, to a group of 6 female sprague Dawley rats at the single dose of 2000 mg/kg body weight. The experimental protocol was established according to the official method as defined in the OECD guideline No. 423 dated December 17th, 2001 and the test method B.1 tris of the council regulation No. 440/2008.

No mortality occured in animals dosed at 300 mg/kg body weight.

No clinical signs related to the adminsitration of the test item were observed during the study.

No body weight evolution of hte animal remained normal throughout the study.

The macroscopic examination of the animal at the end of the study did not reveal treatment related changes.

No mortality occured in animals dosed at 2000 mg/kg body weight.

A decrease in spontaneous activity (3/) and piloerection (3/6) were noted at 1 hour post-dose.

No body weight evolution of hte animal remained normal throughout the study.

The macroscopic examination of the animal at the end of the study did not reveal treatment related changes.

In conclusion, the LD 50 of the test item is higer than 2000 mg/kg body weight by oral route in the rat.

In accordance with the OECD guideline No. 423, the LD50 cut off-of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat.

According to the criteria of classification , packaging and labelling of dangerous substances and preparation in accordance with the ECC Directives 67/548, 2001/59 and 99/45, the test item does not have to be classified. No symbol or risk phrase is required.

In accordance with the regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, the test item does not have to be classified. No signal word or hazard satement is requird.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study is a GLP compliant and has Klimisch score 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:

9 May - 10 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53840 Le Genest St Isle- France)
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: 245 to 271 g (males); 223 to 240 g (females)
- Housing: group, polycarbonate cages with steinless steel mesh lid
- Diet: M20-SDS ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10% of the body surface
- Type of wrap if used: gauze dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.32 ml /kg, equal to 5235 mg/kg bw
the amount applied was calculated based on the density and the concentration of HAPS in the test item

VEHICLE
none

Duration of exposure:

24 hours

Doses:

5235 mg/kg bw (equivalant to 2000 mg/kg compound)

No. of animals per sex per dose:

5 rats/per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily, weighing on day 0, 2, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

mean and standard deviation of body weights

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 235 mg/kg bw

Based on:

test mat.

Remarks on result:

other: as aqueous solution

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

solid

Mortality:

no mortality observed

Clinical signs:

other: no systemic clinical sign was observed. Erythema was noted from 24 hours post-dose in all animals and was totally reversibel on day 7. Scabs were noted in all animals from 48 hours post-dose and remained on day 14 in all animals.

Gross pathology:

no treatment related changes

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study is well performed and gives following results for the Endpoint:
LD 50 (dermal route) > 5235 mg/kg bw to testmaterial (aqueous solution)
LD 50 (dermal route) > 2000 mg/kg bw solid sodium 3-(allyloxy)-2-hydroxypropanesulphonate)

Executive summary:

At the request of the sponsor, the test item sodium 3-(allyloxy)-2-hydroxypropanesulphonate) (HAPS) was applied onto the intact skin of 10 Sprague Dawlley rats (5 males and 5 females) at the single dose of 5235 mg/kg body weight. The experimental protocol was established on the basis of the official method as defined in the OECD guideline No. 402 dated February 24th, 1987 and the test method B.3 of the Council regulation No. 440/2008 of 30 May 2008.

No mortality occured during the study.

No systemic clincal sign related to the administration of the test item was observed.

Erythrema was noted from 24 hours post-dose in all animals and was totally reversible on day 7. Scabs were noted in all animals from 48 hours post-dose and remained on day 14 in all animals.

The body weight evolution of the animals remained normal throughout the study.

The macroscopcal examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD 50 of the test item sodium 3-(allyloxy)-2-hydroxypropanesulphonate) (HAPS) as -aqueous solution -is higher than 5235 mg/kg bodyweight by dermal route in the rat.

In conclusion, the LD 50 of the test item sodium 3-(allyloxy)-2-hydroxypropanesulphonate) (HAPS) as -solid -is higher than 2000 mg/kg bodyweight by dermal route in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Justification for selection of acute toxicity – inhalation endpoint
According to Annex VIII 8.5.2 of regulation (EC) No 1907/2006 testing by the inhalation route is appropiated if exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The test item is marketed in a solution, so the exposure of humans via inhalation is unlikely.

Justification for selection of acute toxicity – dermal endpoint
The study is a GLP compliant and has Klimisch score 1.