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Description of key information

Acute toxicity after single oral application was tested in several tests in which With reference to the most conservative approach for LD50 derivation the study which leads to the lowest limit value is described as follows:
female rats received up to 4000 mg/kg bw. Two females out of ten died at 2000 mg/kg bw, 7 at 2500 mg/kg bw, 7 at 3200 mg/kg bw/d and all animals at 4000 mg/kg bw. The LD50 value for acute oral toxicity was calculated to be 2474 mg/kg bw.

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:
9. Oct 27. Oct 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well reported guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Weight at study initiation: 123.2 g
- Fasting period before study: 16 h
- Housing: in Macolon cages type III (in groups of 1-5 animals)
- Diet (e.g. ad libitum): R10 Alleindiät für Ratten, Ssniff Spezialfutter, Soest, Germany, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09.10. To: 27.10.1986
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: undiluted
- Amount of vehicle (if gavage):3.522 - 5.584 mL/kg


MAXIMUM DOSE VOLUME APPLIED: 5.584 mL/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: dose setting based on results of pre-study
Doses:
3980, 5010 or 6310 mg/kg bw/d
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations daily after application / Weighing once weekly
- Necropsy of survivors performed: yes
Statistics:
LD50 determination according to Litschfield and Wilcoxon
Preliminary study:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 300 mg/kg bw
95% CL:
> 4 609 - <= 6 095
Mortality:
Dose: 3980 mg/kg bw, Mortality rate: 1 / 5 (males), 0/5 (females)
Dose: 5010 mg/kg bw, Mortality rate: 5 / 5 (males), 1/5 (females)
Dose: 6310 mg/kg bw, Mortality rate: 3 / 5 (males), 3/5 (females)
Clinical signs:
other: closed eye lid, abnormal breathing, crouched posture, piloerection, decreased motor acivity all signs were reversible within 48 h
Gross pathology:
thickening/necosis of intestinal and stomach mucosa
necrotic foci in liver, kidneys, spleen, pancreas and testis (sporadically)
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of Phosphoric acid, butyl ester was 5300 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.
Executive summary:

Phosphoric acid, butyl ester was tested for its acute oral toxicity potential. 5 male and 5 female rats were treated with doses of 3980, 5010 or 63100 mg/kg bw and observed for 14 days.

The median lethal dose of Phosphoric acid, butyl ester (LD50) was 5300 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 474 mg/kg bw
Quality of whole database:
Valid with restrictions.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Only one study summary available.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Only two study summaries available.

Additional information

Based on the results of an oral toxicity study the LD50value for acute oral toxicity was calculated to be 2474 mg/kg bw.


According to EU regulation 1907/2006, Annex VII, column 2 an acute dermal or inhalation toxicity study needs not to be conducted sincePhosphoric acid, butyl esteris classified as corrosive to the skin. Furthermore, the results of one available study on acute inhalation toxicity in rats (LC0(1 h exposure) = 20.28 mg/L) and two acute dermal toxicity studies in rabbits (LD50> 2000 mg/kg bw) show the low acute dermal and inhalation toxicity potential.


Justification for selection of acute toxicity – oral endpoint
Well reported guideline study. Valid without restriction. However, in order to follow the most conservation approach the result of an less valid study was considered for LD50 derivation.

Justification for selection of acute toxicity – inhalation endpoint
n.a.

Justification for selection of acute toxicity – dermal endpoint
n.a.

Justification for classification or non-classification

Due to the findings described in the most sensitive acute oral toxicity study (LD50oral in female rats 2474 mg/kg bw) Phosphoric acid, butyl ester does not have to be classified as acute orally toxic. Based on the substance's corrosive properties further acute testing is not mandatory.
Phosphoric acid, butyl ester does not have to be classified as acute toxic.