Registration Dossier

Administrative data

Description of key information

The acute toxicty of the test item was investigated in rats after oral, inhalative and peritoneal administration. In all these tests, no mortalities have been observed

up to the highest dose tested, i.e. the LD50 values exceeded 16000 mg/kg (oral), 5.114 mg/L (inhalative) and 6400 mg/kg (peritoneal), respectively.

Based on this study, the test item is considered to be neither harmful nor toxic after single administration.

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:
1970
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
study was performed before GLP regulation was established
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 113 (100-120) g
- Housing: Makrolon Typ III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature: 25 +/-2°C
- Humidity: 50-55%
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 or 20%
Doses:
800, 1600, 3200, 6400, 12800, 16000 mg/kg body weight
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
The animals were treated by single oral administration (gavage) using a 10 or 20% aqueous DHA solution at the following dose levels: 800, 1600, 3200, 6400, 12500, or 16000 mg/kg bw. The animals were observed for clinical signs and mortality up to 14 days after application. After 14 days all animals were killed and subjected to gross pathological investigation.
Statistics:
No
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality was observed during this study.
Clinical signs:
One hour after test item application the animals of the low and mid dose groups showed drowsiness, staggering, and sporadically dyspnoea. The animals receiving 12500 or 16000 mg/kg bw showed dizziness, dyspnoea, twitching and temporary prone position. After 24 hours no clinical signs were observed anymore.
Body weight:
Body weight was unaffected.
Gross pathology:
Gross pathology did not reveal any abnormalities in rats treated with the test item up to 16000 mg/kg bw.
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the LD50 of the test item in rats after single oral administration was > 16000 mg/kg body weight.
Executive summary:

The acute toxicity potential of the test item was evaluated following single oral administration to male and female Wistar rats at dose levels of 800, 1600, 3200, 6400, 12500 or 16000 mg/kg bw in water. No deaths were observed in any test item group during the 14-day observation period after administration. One hour after treatment the animals of the low and mid dose groups showed drowsiness, staggering, and sporadically dyspnoea. The animals receiving 12500 or 16000 mg/kg bw showed dizziness, dyspnoea, twitching and temporary prone position. After 24 hours no clinical signs were observed in any test item group. Body weight gain of the treated rats was unaffected. Gross pathology did not reveal any abnormalities in rats treated with the test item up to 16000 mg/kg bw.

Based on the results of this study, the maximum non-lethal dose of the test item in rats after single oral administration is >16000 mg/kg bw. Therefore, the test item is considered to have no toxicity potential after single administration by the oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
16 000 mg/kg bw

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
Study period:
2003-12-22 to 2004-05-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted 1981-05-12
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
published 1992-12-29
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
other: Limit test
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd. Laboratory Animal Services, Fuellinsdorf, Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Males: 9 weeks
Females: 11 weeks
- Weight at study initiation: Males: 239.6 - 251.3g
Females: 204.0 - 215.9g
- Fasting period before study:
- Housing: Groups of 5 animals of the same sex were housed in Makrolon type IV cages with wire mesh tops
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 26-51
- Air changes (per hr):
- Photoperiod: 12 hrs dark / 12 hrs light
- Music was played 12h /day mainly during light period
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
2.92 µm
Geometric standard deviation (GSD):
2.41
Remark on MMAD/GSD:
The MMAD values obtained from two gravimetric measurements of particle size distribution were similar:
Impactor 1: MMAD = 2.92 µm [2.41];
Imapctor 2: MMAD = 2.96 µm [2.43]
The MMADs were within the range of 1-4µm as recommended by Guidelines.
Details on inhalation exposure:
A dust aerosol was generated from the test item using a rotating brush aerosol generator (CR 3020, CR Equipments SA, CH-1295 Tannay, Switzerland) connected to a micronising jet mill. No diluent air was added. The generated aerosol was discharged into the exposure chamber through a 63Ni charge neutraliser.
Test atmosphere samples for the gravimetric measurements of the test item concentration and particle size distribution, and for the measurement of relative humidity, temperature and oxygen concentration, were collected directly from the feed tube in the breathing zone of the animals, at an empty port of the exposure chamber delivering "fresh" test item to the animal's nose. This approach was chosen in order to obtain representative samples of what was delivered to the animals. Airflow rates were determined for the recording of relative humidity, temperature and oxygen concentration and during the collection of samples for the determination of test item concentration using a dry-test meter and a pressure gauge (Schlumberger Industries SA, City of Geneva and Timeus & Co., Zurich, respectively), calibrated with a reference dry-test meter. Sampling airflow rates during the collection of impactor samples were determined using a calibrated pressure gauge (Timeus & Co., Zurich).
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric measurement
Duration of exposure:
4 h
Concentrations:
mean aerosol concentration = 5.114 mg/L air
No. of animals per sex per dose:
A group of 5 male and 5 female Wistar rats [HanBrl:WIST(SPF)] was used in this study.
Control animals:
no
Details on study design:
The 10 animals were exposed by nose-only, flow-past inhalation to the test item at a mean aerosol concentration of 5.114 mg/L air for a single 4-hour period. Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters of 2.92 µm and 2.96 µm. All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. On day 15, all animals were sacrificed and necropsied.
Statistics:
No
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was observed.
Clinical signs:
other: No clinical signs were observed.
Body weight:
No relevant adverse effects on body weight development were observed.
Gross pathology:
No macroscopic pathology findings.
Other findings:
no other findings
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the data of this study, the LC50 value of the test item in rats exceed 5.114 mg/L air. No toxicity was observed in rats after inhalation of the test item up to the limit dose.
Executive summary:

The acute toxicity potential of the test item after inhalation was investigated in Wistar rats after an exposure period of 4 hours using a nose-only inhalation system. Male and female animals were exposed to the test item at a mean aerosol concentration of 5.114 mg/L air with a particle size (MMADs) of ~ 2.9 µm. No deaths, no clinical signs and no relevant adverse effects on body weight gain were observed during the 15-day observation period following exposure. Gross necropsy revealed no macroscopic pathological findings, and specifically, no lung or respiratory tract discoloration was observed.

Based on the results of this study, the LC50 of the test item in rats after single exposure by inhalation for 4 hours is >5.114 mg/L, and the test item is considered to have no toxicity potential after single administration by the inhalation route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5.114 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The test item did not show toxicity in acute toxicity tests in rats irrespective of the route of administration used. In an acute oral toxicity study where the test item was given to rats up to 16000 mg/kg, no mortality was observed. No deaths were observed in rats given the test item at dose levels of up to 6400 mg/ kg by the intraperitoneal route, and no toxicity was observed in an acute inhalation study in rats up to the limit concentration of ≥ 5 mg/L air.

Justification for classification or non-classification

Provided information shows that the test material does not need to classified for acute toxicity according to the EU Regulation (EC) No 1272/2008 on Classification,Labelling and Packaging of Substances and Mixtures.