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Administrative data

Description of key information

The test material exhibits low acute toxicity as evidenced by no observations of mortality at the dose of 2000 mg/kg via both the oral and dermal exposure routes. For the inhalation route, no reliable data are available. Since oral and dermal data are available, inhalation data are not required under REACH.

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 January - 02 February 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Also complies with OECD GLP regulations.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
2011-05-19
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): S-10793
- IUPAC nomenclature - Sodium diisobutyldithiophosphinate
- Lot S-20227-170B
- Appearance - White powder with lumps
- CAS No. 13360-78-6
- Molecular Formula - C8H18PS2.Na
- Molecular Weight - 232 g/mole
- Purity 93-94%
- Expiration date of the lot/batch: 16 December 2013
- Storage condition of test material: At room temperature in the dark
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approx. 9-10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Fasting period before study: overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 23.8ºC
- Humidity (%): 32 - 57%
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: From: 17 January - 02 February 2012
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.

VEHICLE: 1% Aqueous carboxymethyl cellulose
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight.

DOSAGE PREPARATION:
The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.
Doses:
2000 mg/kg body weight


No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Salivation was noted in three animals on Day 1. Hunched posture was noted in one animal on Day 1. Three animals appeared to be lean on Day 4, 5 and 6.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with the test material in the rat was carried out following OECD TG 423 and under GLP conditions.

The test material was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Salivation and hunched posture were noted on day 1 and three animals appeared lean on days 4, 5 and 6. No effect on body weight was observed and no abnormalities were found at macroscopic post mortem examination.

The oral LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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:
02 -16 February 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Also complies with OECD GLP regulations.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
2011-05-19
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): S-10793
- IUPAC nomenclature - Sodium diisobutyldithiophosphinate
- Lot S-20227-170B
- Appearance - White powder with lumps
- CAS No. 13360-78-6
- Molecular Formula - C8H18PS2.Na
- Molecular Weight - 232 g/mole
- Purity 93-94%
- Expiration date of the lot/batch: 16 December 2013
- Storage condition of test material: At room temperature in the dark
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individual housing in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 – 23.9ºC
- Humidity (%): 32 – 57%
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: From: 02 -16 February 2012

For logistic reasons the study was rescheduled which cause a delay in the completion time (protocolled 12 February 2012). The later start has no adverse effect on the outcome of the study.
Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

TEST SITE
- Area of exposure: 18 cm² (females), 25 cm² (males)
- % coverage: 10
- Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was cleaned of residual test substance using tap water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight.

VEHICLE
- Concentration (if solution): 1%

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg

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:
Mortality/Viability:Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
None.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and/or chromodacryorrhoea were noted in the majority of animals on Days 1, 2 and/or 3.
Scales, scabs, yellow discoloration, dry appearance and/or fissures were seen in the treated skin-area of the animals during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with the test material in the rat was carried out following OECD TG 402 and under GLP conditions.

The test material was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg bw for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Hunched posture and/or chromodacryorrhoea were noted in the majority of animals on Days 1, 2 and/or 3. Scales, scabs, yellow discoloration, dry appearance and/or fissures were seen the in the treated skin-area of the animals during the observation period. No effect on body weight was observed and no abnormalities were found at macroscopic post mortem examination.

The dermal LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Regarding the oral route of exposure, in the key study (NOTOX 2012), 6 female Wistar rats (2 groups of 3) were fed a single dose of S-10793 (2000 mg/kg) via gavage. In absence of observed mortality, the LD50 was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guidelines, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Concerning the dermal route of exposure, 2000 mg/kg S-10793 was applied to a clipped area of skin 5x7 cm in area on the back of each test subject (5 animals per sex per dose) for a 24 -hour period. Following 14 days of observation, no test-related mortality was observed. The dermal LD50 value of S-10793 for Wistar rats was established to exceed 2000 mg/kg body weight.


Justification for selection of acute toxicity – oral endpoint
No mortality occurred at the dose level of 2000 mg/kg (NOTOX 2012).

Justification for selection of acute toxicity – dermal endpoint
No mortality occurred at the dose level of 2000 mg/kg (NOTOX 2012).

Justification for classification or non-classification

Not classified - Based on available data and/or professional judgment, the classification criteria are not met.