Registration Dossier

Administrative data

Endpoint:
pH
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Information provided by the laboratory before an acute oral toxicity study
Remarks:
No information on method used.
Cross-reference
Reason / purpose:
reference to same study
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
pH measured before an acute oral toxicity study.
GLP compliance:
yes (incl. certificate)
Remarks:
2011-05-19

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
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

Results and discussion

pH value
pH value:
> 7.2 - < 7.9
Concentration:
1 other: % in water

Applicant's summary and conclusion

Conclusions:
The pH of the substance was measured to be 7.2-7.9 at 1% in water.
Executive summary:

The pH of the substance was measured to be 7.2-7.9 at 1% in water.