Barium 4-dodecylphenolate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 value: 300 < LD50 ≤ 2000 mg/ kg bw

Acute dermal toxicity: LD50 value: >2959 mg/ kg bw (equivalent to the limit dose of 2000 mg/kg bw after correction for water content (32.4 %))

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:

2017-11-30 to 2017-12-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2015-06-05

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: dry, < 30°C

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks

- Weight at study initiation: 158 - 177 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: animals were kept in groups of three animals in IVC cages, type III H, polysulphone cages; bedding material: Altromin saw fibre bedding
- Diet (ad libitum, for exception refer to "fasting period before study" above): Altromin 1324 maintenance diet for rats and mice (Altromin Spezialfutter GmbH & Co. KG, Im Seelenkamp 20, 32791 Lage, Germany)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C
- Humidity: 55 ± 10%
- Air changes: 10x/hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Source: Sigma-Aldrich Chemie GmbH, Riedstrasse 2, 89555 Steinheim, Germany
- Justification for choice of vehicle: this vehicle was chosen due to its non-toxic characteristics.
- Lot no.: MKCC0462
- Expiry date: 2018-01-31

Doses:

Starting dose (step 1): 300 mg/kg bw
Step 2: 2000 mg/kg bw
Step 3: 300 mg/kg bw

No. of animals per sex per dose:

9 female rats (3 animals/step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. The animals which had to be sacrificed for ethical reasons or died spontaneously during the observation period were necropsied as soon as they were killed.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Preliminary study:

not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg /kg bw: no animals died
2000 mg/kg bw: all animals died prematurely, one was found death 180 minutes after dosing, the two remaining animals were sacrificed for ethical reasons on test day 2

Clinical signs:

other: 300 mg/kg bw after 0-30 min: slightly reduced spontaneous activity, prone position, slight ataxia, moderate piloerection, moving the bedding after 30-60 min: prone position, moderate ataxia, moderate piloerection, moving the bedding, hunched posture, mode

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 value: 300 < LD50 ≤ 2000 mg/ kg bw
According to the Regulation (EC) NO 1272/2008 and subsequent adaptations, the substance is classified as acute toxic via the oral route (Cat.4; H302).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

one key study available

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-10-05 to 2020-01-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017-10-09

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2019-09-16

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient (21 to 29° C); dry and protected from light in the original container

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: due to the physical-chemical properties of the test item, the test item was stirred and heated to 50 - 55° C for 21 minutes prior to administration in order to facilitate homogenous sampling of the test material. The test material was allowed to cool overnight before application to the animals.

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 2000 mg/kg bw dose level group: 201.68 g to 203.40 g; 2959 mg/kg bw dose level group: 229.24 g to 235.40 g
- Housing: housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill; range finding study: housed individually after treatment throughout the observation; main study: during treatment, the animals were housed individually and after patch removal they were housed together; bedding material: clean sterilized paddy husk; environmental enrichment: paper shredding
- Diet (ad libitum): Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG)
- Water (ad libitum): deep bore-well water passed through Reverse osmosis unit
- Acclimation period: 5 days (range finding study); 11 and 10 days (main study; 2000 and 2959 mg/kg body weight, respectively)

ENVIRONMENTAL CONDITIONS
- Temperature: 19.3 ° C to 22.9° C
- Relative humidity: 42% to 67%
- Air changes: 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST MATERIAL
The first dose level tested was 2000 mg/kg bw of the test item. However, a correction for water content of the test item (32.4%) was not taken into account and the dose level used was not equivalent to a limit dose level of 2000 mg/kg bw (actual received dose: 1352 mg/kg bw after correction for water content). Therefore, further testing at another dose level of 2959 mg/kg (actual dose: 2000 mg/kg bw after correction for water content) was considered necessary.

TEST SITE
- Area of exposure /% coverage/ Type of wrap if used: on the day, before the application of the test item, fur from the dorso-lateral area of the trunk of the animals was removed by clipping closely with an electric hair clipper (approximately 10% of surface area of body). Care was taken to avoid abrading the skin.
Required quantity of the test item per animal (based on the individual animal day 1 body weight) was weighed on to aluminium foil. Prior to the test item application, the treatment area was covered with a nylon mesh in order to facilitate the removal of the test substance. Then, the test item was taken on to porous gauze dressing which was then applied uniformly over an area which is at least 10% of the total body surface area. The porous gauze dressing is then wrapped with non-irritating adhesive tape and finally, the application site was wrapped using crepe bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the residual test item was removed with corn oil from the skin and the skin was dried with absorbent cotton.
- Time after start of exposure: at the end of the contact period

Duration of exposure:

24 hours

Doses:

2000 and 2959 mg/kg bw

No. of animals per sex per dose:

3 females (Range finding study: 1 female; main study: 2 females)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: all the animals were observed for clinical signs of toxicity and mortality at 20 to 30 min, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) post dosing on Day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Furthermore, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize method.
Individual animal body weight was recorded at receipt, on day 1 before test item application, on day 8 and 15 during the experimental period.

- Necropsy of survivors performed: yes, on day 15, all the animals were humanely sacrificed by carbon dioxide asphyxiation and subjected to necropsy and a complete gross pathological examination.

Statistics:

not applicable

Preliminary study:

not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 959 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (equivalent to the limit dose of 2000 mg/kg bw after correction for water content (32.4 %))

Mortality:

- 2000 and 2959 mg/kg bw: no animal died in either the range finding study or the main study animals.

Clinical signs:

other: - 2000 mg/kg bw: erythema was observed from day 2 to day 4 and all the observations reversed back to normal on day 5. - 2959 mg/kg bw: erythema was observed from day 2 to day 6 and all the observations reversed back to normal on day 7.

Gross pathology:

- 2000 and 2959 mg/kg bw: no treatment related gross pathological changes were observed in any of the animals of the range finding study or the main study at any dose level.

Other findings:

Skin reactions:
- 2000 mg/kg bw: very slight erythema (barely perceptible) was observed for the range finding study animal as well as main study animals at the treatment sites at 24 and 48 hours after test item removal. All observations reversed back to normal at 72 hours after removal of test item. No oedema was observed for any animal at 24, 48, and 72 hour observations following test item removal.

- 2959 mg/kg bw: very slight erythema (barely perceptible) was observed in both range finding study and main study animals at the treatment sites at 24, 48 and 72 hour observations after removal of test item. No oedema was observed for any animal at 24, 48, and 72 hour observations following test item removal.

The mean score across scoring times (24, 48 and 72 hours after patch removal) for both range finding study and main test animals was '0.67' for erythema and '0' for oedema for the dose level 2000 mg/kg bw and '1' for erythema and '0' for oedema for the dose level 2959 mg/kg bw.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats) > 2959 mg/kg bw (equivalent to the limit dose of 2000 mg/kg bw after correction for water content (32.4 %))
The substance does not require classification for acute dermal toxicity according to Regulation (EC) No 1272/2008 and its subsequent amendments.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Barium 4-dodecylphenolate

 

One acute toxicity study in rats (key study) via the oral route with Barium 4-dodecylphenolate is available, resulting in a LD50 in the range of 300 to 2000 mg/kg bw.

Barium 4-dodecylphenolate was administered in three steps at doses of 300 and 2000 mg/kg bw to female Wistar Crl:WI (Han) rats. All animals were observed daily for a period of 14 days. Individual body weights were recorded before administration and thereafter in weekly intervals. At the end of the study all animals were sacrificed, dissected and inspected macroscopically. At 300 mg/kg bw all animals survived and no changes in body weight or pathological changes were observed. At 2000 mg/kg bw all animals died prematurely. The LD50 results in a classification of the Barium 4-dodecylphenolate for acute toxicity via the oral route Category 4 and is in line with the legally binding harmonised classification of barium salts ((EC) No 1272/2008; Index No. 056-002-00-7).

One acute toxicity study in rats (key study) via the dermal route with Barium 4-dodecylphenolate is available, resulting in a LD50 greater than 2959 mg/kg bw (equivalent to the limit dose of 2000 mg/kg bw after correction for water content (32.4 %)). Barium 4 -dodecylphenolate was administered to groups of three female Sprague Dawley rats at dose levels of 2000 and 2959 mg/kg bw. All animals were observed daily for a period of 14 days. Individual body weights were recorded at receipt, on day 1 before test item application, on day 8 and 15 during the experimental period. At the end of the study all animals were sacrificed and inspected macroscopically. No animal died during the observation period at any dose level. Erythema was observed from day 2 to day 4 or from day 2 to day 6 at the 2000 and 2959 mg/kg bw dose levels, respectively. The skin reactions were fully reversible on day 5 or 7 at the 2000 and 2959 mg/kg bw dose levels, respectively. No treatment-related effects were observed for body weight or gross pathology at any dose level. Based on these results, no classification for acute dermal toxicity is warranted.

A study for acute toxicity via inhalation was not conducted with Barium 4 -dodecylphenolate, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. However, Barium 4 -dodecylphenolate is classified for acute toxicity via the inhalation route Category 4 due to the legally binding harmonised classification of barium salts ((EC) No 1272/2008; Index No. 056 -002 -00 -7).

Justification for classification or non-classification

Acute oral toxicity The LD50 for Barium 4-dodecylphenolate is 300 < LD50 ≤ 2000 mg/ kg bw, hence the substance is classified as acute toxic via the oral route Category 4 according to the Regulation (EC) 1272/2008 and its subsequent amendments (Cat.4; H302), which is in line with the legally binding harmonised classification of barium salts ((EC) No 1272/2008; Index No. 056-002-00-7).

 

Acute dermal toxicity Barium 4-dodecylphenolate is not acutely toxic via the dermal route based on an acute dermal toxicity test (OECD 402) and does not require classification according to Regulation (EC) No 1272/2008 and its subsequent amendments.

Acute inhalation toxicity A substance specific study for acute toxicity via inhalation is not available, since Barium 4 -dodecylphenolate is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. However, Barium 4 -dodecylphenolate is classified for acute toxicity via the inhalation route Category 4 due to the legally binding harmonised classification of barium salts ((EC) No 1272/2008; Index No. 056 -002 -00 -7).

Specific target organ toxicant (STOT) - single exposure: dermal Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute dermal toxicity test (OECD 402). Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, dermal are not met and Barium 4-dodecylphenolate does not require classification according to Regulation (EC) No 1272/2008 and its subsequent amendments.