Registration Dossier
Registration Dossier
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EC number: 421-720-5 | CAS number: 18085-02-4 3,4-DIACETOXY-1-BUTENE
Endpoint summary
Administrative data
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
- 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.
Reference
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
Additional information
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).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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