Bis(tributyltin) oxide

Endpoint summary

Description of key information

Oral exposure: The LD50 was determined to be 127 mg/kg with confidence limit (95%): 98-165 mg/kg.

Inhalation: Schweinfurth, H. & Schmidt, M. (1986) - Under the test conditions, no effects were reported

Schweinfuth, H et al (1985) (a review) - Based on animal studies exposure to aerosols of test material results in moderate toxicity.  LC50 values for rats ranged from 65-77 mg/m3 (depending on particle size) and in guinea pigs exposed to aerosols of test material in olive oil at 200 mg/m3 and above, no animals survived.  However, rats exposed to saturated vapours of test material for up to 7 h showed no mortality. The lack of mortality in the rat study with saturated vapours should be attributed to the low vapour pressure of the test material rather than to a low degree of inherent toxicity. According to the criteria of the OECD guidelines for testing chemicals (No 403 annex, vapours are unlikely to cause acute inhalation hazard.

Schmidt N (1977) - The results were reported in a non-standard form (ml/m^3). The LC50 was reported as 0.633 mL/m^3. As the aerosol was reportedly produced from a 97.1-97.4 % solution of the test material, presuming this is % weight and not volume, converting this to mg/m^3 would give 6146.43 mg/m^3. (assuming 97.1 g in 100 mL).

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:

From 18 October 1972 to 13 November 1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline available

Principles of method if other than guideline:

A single per os application of ZK 21.955 was given to rats and observations were made.

GLP compliance:

no

Remarks:

Study was completed prior to GLP standards, but would have been substantially in compliance with GLP

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

30 male and 30 female rats, supplied by Dr. Hagemann.
Acclimatized for 9 days.
Caged in Macrolon type II with wire-mesh bottom, 1 animal per cage.
Body weight ranges from 75 to 105 grams for males, and 70 to 95 grams for females
Feed: pelleted Altrmomin R, ad libitum
Water: tap water, ad libitum
Room Temp = 22-24°C
Relative Humidity = 50-63 %
Fasting time prior to application:19 hours
Observation time: 27 days

Route of administration:

oral: gavage

Vehicle:

other: CMC, NaCL, water

Details on oral exposure:

Per os (intragastrically); 1 gram in 100 ml
Formulation: Emulsion; 0.9 g NaCl + 0.5 g CMC + 0.085 g Myrj ad 100 mL dem. water (pH 7.0)

Doses:

Single dose (1 gram in 100 ml)

No. of animals per sex per dose:

30 male and 30 females (only one dose administered)

Control animals:

not specified

Details on study design:

No information

Preliminary study:

No information

Sex:

male/female

Dose descriptor:

LD50

Effect level:

127 mg/kg bw

95% CL:

>= 98 - <= 165

Mortality:

Yes - mortality occurred on day 2-6.

Clinical signs:

other: Apathy of dose-dependent degree, beginning at day 1 and lasting for several days, later on emaciation in single animals; extended abdomen, ruffled fur, paleness.

Gross pathology:

In animals dying before the end of the observation period, congestion, haemorrhages and hemorrhagic erosions of the gastric glandular mucosa, enteritis; haemorrhages, oedema, and emphysema of the lung (after 90 mg/kg and higher). In animals sacrificed at the end of the study, these effects were not seen.

Interpretation of results:

other: Acute toxicity (category 3) according to EU criteria

Conclusions:

LD50 in rats (per os) = 127 mg/kg
confidence limit (95%): 98-165 mg/kg

Executive summary:

Animals received a single dose of test material, orally (by gavage) and observations were made. Apathy of dose-dependent degree, beginning at day 1 and lasting for several days, later on emaciation in single animals; extended abdomen, ruffled fur, paleness. Mortality occurred on day 2-6. In animals dying before the end of the observation period, congestion, hemorrhages and hemorrhagic erosions of the gastric glandular mucosa, enteritis; hemorrhages, edema, and emphysema of the lung (after 90 mg/kg and higher). In animals sacrificed at the end of the study, these effects were not seen.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

127 mg/kg bw

Additional information

Oral:

Gunzel & Khater (1973) was selected as the key study for this data requirement. The method was considered comparable to harmonised guidelines and when assessed in line with GLP criteria, the study was considered to have been performed in line with GLP principles with acceptable deviations (as the study was written prior to the development and enforcement of GLP).

 

Four further studies were provided as supporting information, as the supporting studies were available as short abstracts, they were assigned a reliability score of 4 as it was not possible to assess the reliability of the data based on the limited level of reporting. The supporting studies were; Schobel C. (1986), Schweinfuth H et al (1986), Gunzel P & Keil (1971) and Gunzel P & Keil (1971) (the two Gunzel P & Keil (1971) studies were performed at different dosing concentrations.).

 

Inhalation:

All studies were provided for information purposes only. The three available studies were either not sufficient or not adequate for assessment as stand-alone studies or as a weight of evidence.

Schweinfurth, H. & Schmidt, M. (1986) was assigned a reliability score of 3 due to methodological deficiencies in analytical procedures for determining concentration levels in test atmospheres. Schweinfuth, H et al (1985) was assigned a reliability score of 4 as it is a review of previous works and is reported in a limited level of detail making it impossible to assess the reliability of the data. Schmidt N (1977) was performed to a good standard and was assigned a reliability score of , however, the substance was tested as an aerosol. Since the substance is not made into an aerosol under normal and reasonably foreseeable use, and the only possible occurence of inhalatiobna exposure is by air contamination of substance vapours, the effects seen in this study do not quantify the inhalation risk of the compound in practice.

 

Dermal:

All studies were provided for information purposes only. None were suitable for addressing the acute dermal endpoint. Schweinfurth. H et al (1986), Gunzel & Richter (1970), Gunzel & Keil (1971), Plum D (1979) were all assigned a reliability score of 4 (not assignable) due to insufficient detail in the reporting of the study.

Justification for classification or non-classification

The substance is included in the group of substances "tributyltin compounds" which is itself included in Annex VI to Regulation (EC) No 1272/2008 with Index Number 050-008-00-3. The entry has been assigned the hazard classification of Acute toxicity 3 (oral) and Acute toxicity 4 (dermal) with the resulting hazard statements of H301: toxic if swallowed and H312: harmful in contact with skin.

The available data on acute oral toxicity substantiate classification as acute toxicity 3 (oral).