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Diss Factsheets

Administrative data

Description of key information

In a study conducted in male rats, an oral LD50 = 1530 mg/kg bw was found. This value is supported by several other studies in which a LD50 value was found in a similar range, however these studies are not reliable due to limited documentation.

In a valid study for acute inhalation toxicity a LC50 > 2.14 mg/L (highest technically feasible concentration) was found. All animals (except one) survived the post-exposure period. Clinical signs and necropsy revealed no indication that this concentration might be fatal. Therefore it can be concluded, that the LC50 value is much higher than the technically feasible concentration of the experiment. A classification for acute inhalation toxicity is no justified. No valid studies are available with dermal exposure. From 2 not reliable studies, a dermal LD50 > 3160 mg/kg bw and > 10000 mg/kg bw was indicated.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Gross or histopathological examination was not performed, big volumes of DMSO was used as a solvent
Principles of method if other than guideline:
Ten male rats/dose (bw: ca. 160-180 g), single oral application by gavage, substance dissolved in DMSO (2 ml/100 g bw), observation time: 14 d, calculation of LD50 according to Fink (1965) Arzneim.-Forsch. 15, 624
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
male Wistar-II-rats, SPF, weight 160 - 180 gr, husbandry: 5 animals per cage
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
no further data
Doses:
100, 500, 1000, 2000, 3100, 5000 mg/kg bw in DMSO
No. of animals per sex per dose:
10 males per dose
Control animals:
not specified
Details on study design:
No further data
Statistics:
According Fink and Hund, Arzneimittelforsch. (1965), 15, 624
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 530 mg/kg bw
Mortality:
Dose 100 mg/kg, mortality 0/10; dose 500 mg/kg, mortality 2/10; dose 1000 mg/kg, mortality 2/10, dose 2000 mg/kg, mortality 4/10; dose 3100 mg/kg, mortality 9/10; dose 5000 mg/kg, mortality 10/10
Clinical signs:
other: Sedation, disturbances of equilibrium
Gross pathology:
no data
Other findings:
See: Any other information on results including tables

Dose-group, time of death, No of rats which died, No of rats with symptoms:
100 mg/kg bw, no deaths, 0/10, 0/10
500 mg/kg bw, 3-4 d, 2/10, 10/10
1000 mg/kg bw, 3 d, 2/10, 10/10
2000 mg/kg bw, 2-3 d, 4/10, 10/10
3100 mg/kg bw, 2-3 d, 9/10, 10/10
5000 mg/kg bw, 2 d, 10/10, 10/10
Symptoms: sedation, imbalance, and bloody eyes.
No gross or histopathological examination.

Interpretation of results:
Category 4 based on GHS criteria
Executive summary:

Method: single orale application per gavage of test substance (dose 100, 500, 1000, 2000, 3100, 5000 to 10 male rats, post-observation time 14 days)

Result: LD50 = 1530 mg/kg bw (male rats)

Reference: Loeser (Bayer AG), 1978

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 530 mg/kg bw
Quality of whole database:
Scientifically acceptable and sufficient for assessment

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Ten healthy rats (5/sex) were exposed nose-only to a test atmosphere of phthalic anhydride of 2.14 mg/L (highest technically feasible concentration) for 4 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure or until death occurred. Body weights were recorded prior to exposure and again on Days 7 and 14 (termination) or after death. Necropsies were performed on all animals.
GLP compliance:
yes
Test type:
other: highest technically feasible concentration used
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.14 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.14 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h

One male died upon chamber removal. There were no clinical signs noted for this animal prior to death. Following exposure, the clinical signs observed for the surviving animals included hypoactivity, abnormal respiration, reduced fecal volume, ocular discharge and facial and/or anogenital staining. However they recovered by Day 14. Although three animals lost weight by Day 7, all surviving animals gained body weight over the 14-day observation period. Gross necropsy of the decedent revealed discoloration of the lungs and liver. No gross abnormalities were noted for any of the euthanized animals when necropsied at the conclusion of the 14-day observation period.

Interpretation of results:
GHS criteria not met
Conclusions:
The exact LC50 cannot be determined.
LC50 > 2.14 mg/L (aerosol) - highest technically feasible concentration.
Executive summary:

Method: according OECD 403 - ten healthy rats (5/sex) were exposed nose-only to a test atmosphere of phthalic anhydride of 2.14 mg/L (highest technically feasible concentration) for 4 hours.

Result: LC50 > 2.14 mg/L (aerosol) - following exposure, the clinical signs observed for the surviving animals included hypoactivity, abnormal respiration, reduced fecal volume, ocular discharge and facial and/or anogenital staining. However they recovered by Day 14. Although three animals lost weight by Day 7, all surviving animals gained body weight over the 14-day observation period. Gross necropsy of the decedent revealed discoloration of the lungs and liver. No gross abnormalities were noted for any of the euthanized animals when necropsied at the conclusion of the 14-day observation period.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 140 mg/m³ air
Quality of whole database:
GLP guideline study

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a study conducted in male rats, an oral LD50 = 1530 mg/kg bw was found. This value is supported by several other studies in which a LD50 value was found in a similar range, however these studies are not reliable due to limited documentation.

In a valid study for acute inhalation toxicity a LC50 > 2.14 mg/L (highest technically feasible concentration) was found. All animals (except one) survived the post-exposure period. Clinical signs and necropsy revealed no indication that this concentration might be fatal. Therefore it can be concluded, that the LC50 value is much higher than the technically feasible concentration of the experiment. A classification for acute inhalation toxicity is no justified.

No valid studies are available with dermal exposure. From 2 not reliable studies, a dermal LD50 > 3160 mg/kg bw and > 10000 mg/kg bw was indicated.

Justification for classification or non-classification

An LD50 of 1530 (oral, rat, male) was found in a valid study, therefore a classification Category 4, H302 is justified.

Due to the result of a valid acute inhalation toxicity study and by a weight of evidence consideration of the acute dermal toxicity studies, a classification is not justified.