1,2-diacetoxybut-3-ene

Endpoint summary

Description of key information

ECHA has provided a 28 day repeated dose study to rats via oral exposure. No studies assessing inhalation or dermal exposure are available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data migrated from NONS with permission to refer granted by ECHA.

Qualifier:

according to guideline

Guideline:

other: 92/69/EEC

GLP compliance:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

28 days

Frequency of treatment:

7 days per week

Dose / conc.:

0 mg/kg bw/day (nominal)

Dose / conc.:

75 mg/kg bw/day (nominal)

Dose / conc.:

225 mg/kg bw/day (nominal)

Dose / conc.:

750 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 male and female animals at each dose group

Control animals:

yes, concurrent vehicle

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Decreased faeces were observed in all rats that received 750 mg/kg/day and sialorrhea was observed in all treatment groups.

Mortality:

mortality observed, treatment-related

Description (incidence):

In animals that received 750 mg/kg/day 1 male was found dead on Day 3 and 1 male was sacrificed as moribund on Day 11.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

In males that received 750 mg/kg/day, mean bodyweights were significantly lower than in controls.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

effects observed, treatment-related

Description (incidence and severity):

Food consumption for males that received 750 mg/kg/day was reduced on Days 4 and 7.

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Alkaline phosphatase (ALP) and ALAT concentrations were increase in males that received 750 mg/kg/day. A slight, statistically significant increase in ALAT was also observed in males that received 225 mg/kg/day. The slight increases in ALAT and ALP could be related to the changes observed in the pancreas of animals that received 750 mg/kg/day.

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

In males that received 750 mg/kg/day, there were increases in relative adrenal, testes, kidney and liver weights and decreased absolute spleen, kidney and thymus weights. Liver weights were also increased in females that received 750 mg/kg/day. No associated gross or microscopic findings were observed in these organs.

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Mild exocrine cell necrosis of the pancreas was observed in animals that received 750 mg/kgbw.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

225 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

not specified

Basis for effect level:

histopathology: non-neoplastic

Dose descriptor:

NOEL

Effect level:

< 75 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: Lack of toxicologically significant effects

Critical effects observed:

yes

Lowest effective dose / conc.:

750 mg/kg bw/day (nominal)

System:

other: Pancreas

Organ:

pancreas

Treatment related:

yes

Dose response relationship:

no

Relevant for humans:

not specified

Conclusions:

Based on information provided by ECHA, the results of a 28 day repeated dose study include a NOAEL of 225 mg/kg/day based on effects observed in the pancreas of high dose animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

225 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Study provided by ECHA from NONS dossier.

System:

other: Pancreatic

Organ:

pancreas

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on information provided by ECHA, the results of a 28 day repeated dose study include a NOAEL of 225 mg/kg/day based on effects observed in the pancreas of high dose animals. In animals that received 750 mg/kg/day effects were observed on bodyweight gain, food consumption, liver enzymes and increases in various organ weights. The main effect was observed in males receiving 750 mg/kg/day which included mild exocrine necrosis of the pancreas which may have been related to the change in liver enzymes ALP and ALAT.

The effects on bodyweight, food consumption, organ weights and evidence of minor clinical signs (e.g. decreased faeces) were all considered of low toxicological importance. The organ weight change was present with no evidence histopathologically of organ dysfunction. As the main effect observed in the pancreas was mild and only observed at a high dose (greater than the guidance cut-off values in Tables 3.9.2 and 3.9.3 of the CLP regulation) no classification for STOT RE effects in the pancreas are deemed appropriate in accordance with the CLP Regulation (EC No. 1272/2008, as amended).