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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Slight modifications in selection of dose intervals and the number of exposed animals
Principles of method if other than guideline:
Only 3 animals were dosed at the lowest dose level 300 mg dry weight/kg. The test procedure does not follow completely the minimum requirements of the numbers of test animals for classification purposes in the Globally Harmonised System (GHS).
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Sulfite liquors and Cooking liquors, green
EC Number:
268-612-2
EC Name:
Sulfite liquors and Cooking liquors, green
Cas Number:
68131-30-6
Molecular formula:
HNa3OS
IUPAC Name:
Aqueous alkaline solution of sodium salts produced by dissolving melt from incineration of spent liquor from sodium based pulping processes.
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report):
- Substance type: UVCB
- Physical state: liquid
- Composition of test material, percentage of components: Dry solids content 234 g/l, (180 mg/mL dry solids)
- Lot/batch No. :2013-w39 GL4 After sludge removal before slaker
- Expiration date of the lot/batch:September 2018
- Stability under test conditions: stabile
- Storage condition of test material: stored at room temperature and in the dark
- Other: Ten (10) mL of test item was transferred to a suitable glass beaker. The pH of the test item was adjusted to 10.5 ± 0.1 with 5M HCl. Following adjustment of the pH, purified water was added to give a total volume of 13 mL. As precipitation was observed, the dose formulation was heated carefully until no precipitate was observed. However, it was not possible to dissolve the precipitate by heat, but the dosed formulations were homogeneous.Dilution caused by addition of the HCl solution and water was taken into account in calculations of the dose concentration used for dosing, All preparations were prepared in glass containers. The prepared dose formulations, as pH was adjusted, were used as soon as possible (latest within 24 hours). Any contact of the test item with open air was restricted (by stoppers and minimising the headspace air).

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HanTac:WH (GALAS) from Taconic Europe A/S, Ejby, Denmark
- Age at study initiation: 8-10 weeks
- Weight at study initiation:147 to 186 grams
- Fasting period before study: On the day of dosing the animals were fasted overnight and the food was withheld for a further 3-4-hour period following treatment
- Housing: The rats were kept in transparent polycarbonate cages (floor area: 1500 cm² - Height 21 cm) with either one or two rats in each cage during the acclimatisation period. The cages were cleaned and the bedding changed twice per week. Bedding in sawdust "Jeluxyl" from Jelu Werk GmbH, Josef Ehrler GmbH & Co KG, Ludwigsmühle, D-73494 Rosenberg, Germany.
- Diet (e.g. ad libitum):Altromin 1314 Fortified ad libitum
- Water (e.g. ad libitum):Animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): a cycle of 12 hours light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
pH adjusted to 10.5 prior to administration
Details on oral exposure:
Material dosed as supplied, pH adjusted to 10.5 to avoid corrosive effects in animals. Dose concentration based on the formulation contains approximately 80% (w/w) water corresponding to 234 mg dry weight/mL (assumed density approximately 1.170 g/mL (at 20 °C))
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A single oral dose was administered to the animals by oral gavage.
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The dose volume was calculated according to the most recent body weight data.
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Dosing in each group was performed sequentially meaning that only one animal was dosed on the first day. When no signs of evident toxicity were observed after treatment, the remaining animals in the group were dosed the following day.
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As there were no pre-terminated or moribund animals following dosing in Group 1 (receiving 300 mg dry weight/kg), Group 2 was dosed with 2000 mg dry weight/kg.
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The first day of treatment in each group was designated Day 1. Thereby the first animal in each group was dosed on Day 1 and the remaining two animals on Day 2. However animal Nos 5 and 6 in Group 2 were first dosed on Day 3, as they were not fasted overnight from Day 1 to Day 2.
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All animals were observed for 7 days following dosing.
Doses:
2000 mg/kg, 500 mg/kg, 300 mg/kg
No. of animals per sex per dose:
2 female animals - 2000 mg/kg
1 female animal - 500 mg/kg
3 female animals - 300 mg/kg
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD100
Effect level:
< 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 500 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
ca. 300 mg/kg bw
Based on:
test mat.
Clinical signs:
No clinical signs of evident acute toxicity were observed among the animals treated with 300 mg dry weight/kg. Following treatment with 500 and 2000 mg dry weight/kg signs of evident acute toxicity were observed in the dosed animals. These signs were considered to be related to treatment with the test item and resulted in pre-scheduled termination of the two animals dosed at 2000 mg dry weight/kg.

Group 1 (300 mg dry weight/kg)
Animal No 1
5 minutes after treatment: Slight piloerection.
Animal No 2
No adverse clinical signs.
Animal No 3
5 minutes after treatment: Less active.

Group 2
Animal No 4 (2000 mg dry weight/kg)
2 minutes after treatment: Passive, forced respiration, muscle shivering.
5 minutes after treatment: No respiration, terminated.
Animal No 5 (2000 mg dry weight/kg)
1 minute after treatment: Uncoordinated movements, lying on its side, no muscle tonus, terminated.
Animal No 6 (500 mg dry weight/kg)
1 minute after treatment: Less active, uncoordinated movements.
4-6 minutes after treatment: Lying passive, little movement, forced respiration, pinched abdomen.
10 minutes after treatment: Passive, subdued, pinched abdomen.
20 minutes after treatment: Less active, slight piloerection, pinched abdomen.
1 and 3 hours after treatment: Less active.
Body weight:
At the dose level 300 and 500 mg dry weight/kg, no test item related effect was seen on the body weight. The animals gained weight from dosing until necropsy.
Gross pathology:
No macroscopic findings were observed in any of the animals at necropsy.

Any other information on results incl. tables

Dose 2000 mg dry weight/kg The first animal (animal No 4) dosed at 2000 mg dry weight/kg was, 2 minutes following dosing, passive and had forced respiration and muscle shivering. Five (5) minutes following dosing, no respiration could be observed and it was decided to terminate the animal based on the observed clinical signs. The second animal (animal No 5) dosed with the same dose had 1 minute following dosing uncoordinated movements and was lying on its side. Furthermore, the animal had no muscle tonus. Based on the observed clinical signs, it was decided to terminate the animal 1 minute after dosing.

Dose 500 mg dry weight/kg Following dosing with a dose at 500 mg dry weight/kg, the animal was less active and had uncoordinated movements 1 minute after dosing. Approximately 5 minutes after dosing, the animal was lying passive with little movement and had forced respiration together with a pinched abdomen. The animal was 10 minutes after dosing passive and subdued and had pinched abdomen. Twenty (20) minutes after dosing, the animal was less active and had slight piloerection together with a pinched abdomen. The animal was observed as less active at 1 and 3 hours after dosing. Six (6) hours after dosing and throughout the remaining part of the observation period, no clinical signs were observed.

Dose 300 mg dry weight/kg Following dosing at 300 mg dry weight/kg, one animal showed slight piloerection and another animal was less active 5 minutes after dosing. Ten minutes after dosing and throughout the remaining part of the observation period, no clinical signs were observed. No clinical signs were observed in the remaining animal dosed at 300 mg dry weight/kg.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was toxic to tested animals. As only 3 animals were dosed at the dose level 300 mg dry weight/kg the test item could not be reliable classified to acute toxicity categories according to the CLP/Globally Harmonised System (GHS).
Executive summary:

Under the experimental conditions of this study, it was found that no signs of evident acute toxicity were observed in the three rats receiving a single oral dose of GL4(SA) at 300 mg dry weight/kg. At doses of 500 and 2000 mg dry weight/kg signs of evident acute toxicity were observed in the treated animals. The signs lead to pre-scheduled termination of the two animals receiving 2000 mg dry weight/kg whereas the animal receiving 500 mg dry weight/kg recovered.